Nanotechnology and Nanotechnology and Occupational Safety and Health: Occupational Safety and Health:

What Do We Know?What Do We Know?Charles L. Geraci, Ph.D., CIHCharles L. Geraci, Ph.D., CIH

Centers for Disease Control and PreventionCenters for Disease Control and PreventionNational Institute for Occupational Safety and HealthNational Institute for Occupational Safety and Health

The findings and conclusions in this presentation have not been The findings and conclusions in this presentation have not been formally formally disseminated by the National Institute for Occupational Safety adisseminated by the National Institute for Occupational Safety and Health and nd Health and

should not be construed to represent any agency determination orshould not be construed to represent any agency determination or policypolicy

Environmental Health and Safety PanelEnvironmental Health and Safety Panel2008 International Conference on Nanotechnology for the Forest Products Industry

June 25, 2008

Nanotechnology: The Fast DefinitionNanotechnology: The Fast DefinitionManipulating matter at the atomic levelManipulating matter at the atomic levelCreating materials that have new and unique properties Creating materials that have new and unique properties because of their size.because of their size.

Creating structure and function in the nanometer rangeCreating structure and function in the nanometer range

Richard Smalley Nobel Prize Winner, Chemistry (1996)

Nanotechnology:

“The art and science of building stuff that does stuff at the nanometer scale”AKA: Material science, one molecule at a time.(1943 - 2005)

Current Uses and Applications of Nanotechnology

AgricultureAgriculture Pesticides and fertilizersPesticides and fertilizers

AutomotiveAutomotive composites, epoxies, filmscomposites, epoxies, films

BiomedicalBiomedical diagnostics, drug deliverydiagnostics, drug delivery

ChemicalChemical catalysts, polymer films, coatingscatalysts, polymer films, coatings

ElectronicsElectronics catalysts, polymer films, coatings, fiber opticscatalysts, polymer films, coatings, fiber optics

EnergyEnergy catalysts, lithium batteries, fuel additivescatalysts, lithium batteries, fuel additives

EnvironmentalEnvironmental sensors, catalystssensors, catalysts

FoodFood additives, packaging materials, antimicrobialadditives, packaging materials, antimicrobial

HouseholdHousehold antimicrobials, cleaners, coatings, appliancesantimicrobials, cleaners, coatings, appliances

Personal CarePersonal Care cosmetics, sunscreens, hair/skin productscosmetics, sunscreens, hair/skin products

SportsSports composites for bats and golf clubs, shoescomposites for bats and golf clubs, shoes

TextilesTextiles water/stain resistance, wrinklewater/stain resistance, wrinkle--free, fire free, fire resistanceresistance

Nanotechnology and Occupational HealthNanotechnology and Occupational Health

Nanotechnology Nanotechnology -- The MotivationThe MotivationPurposelyPurposely engineeredengineered for their unique and sizefor their unique and size--dependent properties and behavior.dependent properties and behavior.

Nanotechnology Nanotechnology -- The ChallengeThe ChallengeDo these new Do these new ‘‘nanonano’’ materials present new materials present new safety and safety and health riskshealth risks??How can the benefits of nanotechnology be realized How can the benefits of nanotechnology be realized while proactively while proactively minimizing the potential riskminimizing the potential risk??

The Focus: Free Engineered NanoscaleParticulate Matter–“Nanoparticles”

Not firmly attached to a surface

Not part of a bigger item (e.g.,microchip, cell wall)

Can result in exposure viainhalation, skin absorption oringestion (or other nanospecificroutes of exposure!)

Nanotechnology: Are There Risks?Nanotechnology: Are There Risks?

RISK = HAZARD X EXPOSURERISK = HAZARD X EXPOSURE

HazardHazard:: Biological activity Biological activity –– toxicity. What is known and is toxicity. What is known and is there anything new ?there anything new ?

ExposureExposure: : Where, to what, to what extent, and can it be Where, to what, to what extent, and can it be measured?measured?

Unknowns and uncertainties + rapidly evolving technology Unknowns and uncertainties + rapidly evolving technology = = Risk Management approachRisk Management approach

Key Elements of Key Elements of Risk ManagementRisk Management

Hazard IdentificationHazard Identification““Is there reason to believe this Is there reason to believe this

could be harmful?could be harmful?””

Risk ManagementRisk Management““Develop procedures to minimize Develop procedures to minimize

exposuresexposures””

Exposure AssessmentExposure Assessment““Will there be exposure in realWill there be exposure in real--

world conditions?world conditions?””

Risk CharacterizationRisk Characterization““Is substance hazardous Is substance hazardous andand will will

there be exposure?there be exposure?””

NIOSH Goals Involving NanotechnologyNIOSH Goals Involving Nanotechnology

Hazard AssessmentHazard Assessment: Determine whether nanoparticles : Determine whether nanoparticles and nanomaterials pose risk of injuries and illnesses to and nanomaterials pose risk of injuries and illnesses to workersworkers

Risk AssessmentRisk Assessment: Conduct research to develop a dose: Conduct research to develop a dose--response value and any correlation to human experienceresponse value and any correlation to human experience

Risk ManagementRisk Management: Promote healthy workplaces through : Promote healthy workplaces through interventions, recommendations, and capacity buildinginterventions, recommendations, and capacity building

CollaborationCollaboration: Enhance global workplace safety and : Enhance global workplace safety and health through national and international collaboration on health through national and international collaboration on nanotechnologynanotechnology

What is Needed:What is Needed:

Good ScienceGood ScienceThe Right ScienceThe Right ScienceProper InterpretationProper InterpretationShare and ApplyShare and Apply

Key areas of NIOSH research supporting Key areas of NIOSH research supporting the Risk Management processthe Risk Management process

Hazard IdentificationHazard Identification““Is there reason to believe Is there reason to believe

this could be harmful?this could be harmful?””

Hazard CharacterizationHazard Characterization““Under what conditions could Under what conditions could

it be harmful?it be harmful?””

Exposure AssessmentExposure Assessment““Will there be exposure in Will there be exposure in

realreal--world conditions?world conditions?””

Risk CharacterizationRisk Characterization““Is substance hazardous Is substance hazardous andand

will there be exposure?will there be exposure?””

Risk ManagementRisk Management““Develop procedures to Develop procedures to

minimize exposuresminimize exposures””

ToxicologyToxicologyHealth Effects AssessmentHealth Effects AssessmentSafety ResearchSafety Research

ToxicologyToxicologyField AssessmentField AssessmentChemical and Physical CharacteristicsChemical and Physical Characteristics

Field Exposure AssessmentField Exposure AssessmentProcess DescriptionsProcess DescriptionsControl Technology ResearchControl Technology ResearchPersonal Protective Equipment (PPE) Personal Protective Equipment (PPE) ResearchResearch

Risk AssessmentRisk Assessment-- Dose and DurationDose and DurationDose ModelingDose ModelingExposure CharacterizationExposure Characterization

Risk CommunicationRisk CommunicationGuidance DocumentsGuidance DocumentsInformation DisseminationInformation Dissemination

Challenge: The diversity of “Nanomaterial Production and Use”

TransportTransport

CommercialCommercialAcademicAcademic

Incorporation in ProductsIncorporation in ProductsMaintenance of ProductsMaintenance of ProductsManipulation of ProductsManipulation of ProductsApplication of Products Application of Products -- Medical DeliveryMedical Delivery

Disposal / End of LifeDisposal / End of Life

RecyclingRecycling

Research LaboratoriesResearch LaboratoriesWarehousing/MaintenanceWarehousing/MaintenanceWaste HandlingWaste Handling

Start Up/Scale Up OperationsStart Up/Scale Up OperationsTransportTransportWarehousing/MaintenanceWarehousing/Maintenance

Warehousing/MaintenanceWarehousing/MaintenanceTransportTransportWaste HandlingWaste Handling

Manufacturing/ProductionManufacturing/Production

To evaluate the ‘workplace’, A Life Cycle Approach is needed.

TransportTransport

CommercialCommercialAcademicAcademic

Incorporation in ProductsIncorporation in ProductsMaintenance of ProductsMaintenance of ProductsManipulation of ProductsManipulation of ProductsApplication of Products Application of Products -- Medical DeliveryMedical Delivery

Disposal / End of LifeDisposal / End of Life

RecyclingRecycling

Research LaboratoriesResearch LaboratoriesWarehousing/MaintenanceWarehousing/MaintenanceWaste HandlingWaste Handling

Start Up/Scale Up OperationsStart Up/Scale Up OperationsTransportTransportWarehousing/MaintenanceWarehousing/Maintenance

Warehousing/MaintenanceWarehousing/MaintenanceTransportTransportWaste HandlingWaste Handling

Manufacturing/ProductionManufacturing/Production

To evaluate the ‘workplace’, a Life Cycle Approach is needed.

Knowledge of Toxicity

Low

High

???

NanotoxicologyNanotoxicology

““Are nanoparticles hazardous?Are nanoparticles hazardous?””

Predicted Deposition of Inhaled Particles in theHuman Respiratory Tract

ICRP (1994) model: adult, nose breathing, at rest

Diameter (µm)

Dep

ositi

on P

roba

bilit

y

0.0001 0.001 0.01 0.1 1 10 100

Total

Tracheo-bronchial

Head airways Alveolar

1.0

0.8

0.6

0.4

0.2

0.0

Parameters That Could Affect Parameters That Could Affect Nanoparticle ToxicityNanoparticle Toxicity

SizeSizeShapeShapeCompositionCompositionSolubilitySolubilityCrystalline structureCrystalline structureChargeChargeSurface characteristicSurface characteristicAttached functional groupsAttached functional groupsAgglomerationAgglomerationImpuritiesImpurities

Many may be the metrics for both hazard and exposure determination

Surface AreaHow to Assess Biologic Activity of Nanoparticles?

Fraction of atoms on the surface for a simple cubic lattice with 1 Å bond length

0

0.1

0.2

0.3

0.4

0.5

1 10 100 1000 10000Size (nm)

Frac

tion

of s

urfa

ce a

tom

s

Surface atomsCore atoms

Surface Area as a Dose MetricSurface Area as a Dose Metric• Toxicity of ultrafineTiO2 appears muchhigher than fine TiO2per unit mass

• Toxicity is equivalentwhen surface area isthe exposure metric

Measured polymorphonuclearneutrophils in lung lavage fluid, an indexof inflammation

Oberdorster, Int Arch Occup Environ Health. 2001 Jan;74(1):

Is one of these workers at greater risk for disease?

Bulk Material Nano Sized Particles

Current Research Results Single-Walled Carbon Nanotube Toxicity to Respiratory Tract

Rat lung cells cannot digest and clear long carbon nanotubes.D. Brown, Napier Univ. and I. Kinloch, Univ. Manchester

V. Castranova, NIOSH

Poland, et al: Nature NanotechnologyMay, 2008

Intraperitoneal injection of MWCNTs to investigate possible mesothelial injury• Pathogenic behavior related to length• Inflammation and formation of granulomas• Long CNT fibers more active that short fibers or bundles• Mimics the same processes as asbestos ?

• Starting point: short-term study• Does not address migration from lung to mesothelium

Until more research can be conducted, a prudent approach is warranted

“Using Graphite OEL as an exposure guideline would be inappropriate”

Hazard and Risk Picture - Carbon Nanotubes

Graphics courtesy of AndrewMaynard and Anna Shvedova

Aspiration of SWCNT resulted in:Rapid but transient inflammation and damage

Granulomas and fibrosis at deposition sites of largeagglomerates of SWCNT

Rapid and progressive interstitial fibrosis at depositionsites of dispersed SWCNT

Results were verified with inhalation studyMessage:

•SWCNTs more fibrogenic than an equal mass of ultrafine carbon black or fine quartz.

•Doses approximated exposure at the PEL for graphite (5 mg/m3) for 20 days

Message: The PEL for the ‘large’ form of a materialmay not be a good guide for the nano form.

Risk Assessment: Ultrafine (Nano) TiORisk Assessment: Ultrafine (Nano) TiO22

NIOSH draft recommended exposure limits NIOSH draft recommended exposure limits (RELs):(RELs):1.5 mg/m3 fine TiO2; 1.5 mg/m3 fine TiO2; 0.1 mg/m3 ultrafine TiO20.1 mg/m3 ultrafine TiO2Reflects greater inflammation & tumor risk Reflects greater inflammation & tumor risk of ultrafine on mass basisof ultrafine on mass basiswww.cdc.gov/niosh/review/peer/tio2/www.cdc.gov/niosh/review/peer/tio2/

Same message:Same message: The OEL for a material in its The OEL for a material in its ‘‘largelarge’’ form form may not be appropriate for the Nano formmay not be appropriate for the Nano form

Metrics and MeasurementsMetrics and Measurementsfor Exposure Assessmentfor Exposure Assessment

“Can nanoparticles be measured?”

Nanoparticles: Many shapes, many chemistries

Not all nanoparticles are the same

Carbon Nanotube Air SampleWhich metric to use?

0.18 – 0.32 μm aerodynamic diameter

CNT agglomerates

compact carbon particle

dense nanotube rope

Exposure: Where to Start?Exposure: Where to Start?

Starting Point

TEM analysis of aerosolMass, Size Distribution,Surface Area, Etc.

The Hard WayThe Hard Way

Examples of NIOSH Field Investigations

Type of Facility Type of Particle, Morphology

Size of Particle Range of “Potential” Exposure Concentrations

University Research lab

Carbon Nanofibers Approx. 100 nm diameter, 1-10 microns long

60-90 µg/m3

Metal Oxide Manufacturer

TiO2, Lithium Titanate, powder

100-200 nm <100 nm: 1.4 µg/m3 (TiO2)Total dust: 4-149 µg/m3 (TiO2)<100 nm: ND (Li)Total dust: ND -3 µg/m3 (Li)

Manufacturer Carbon Nanofibers Approx. 100 nm diameter, 1-10 microns long

15 - 1800 µg/m3

Research and Development lab

Quantum Dots, spheres

2 -8 nm ND

Metal Oxide Manufacturer

Manganese, Silver, Nickel, Cobalt, Iron oxides, spheres

8 -50 nm 67 - 3619 µg/m3

Research and Development lab (Pilot-Scale)

Aluminum, spheres 50 – 100 nm 40 - 276 µg/m3

Research and Development lab

Elemental Metals -Silver, Copper, TiO2

15 – 40 nm ND

Filter Media Manufacturer

Nylon 6 Nanofiber 70 - 300 nm diameter, continuous length

ND

Did you detect the Engineered Did you detect the Engineered NanoparticleNanoparticle of Interest?of Interest?

What are the limits of What are the limits of engineering controls and PPE engineering controls and PPE with respect to engineered with respect to engineered

nanoparticles?nanoparticles?

“Can nanoparticles be controlled?”

Conventional Controls Should WorkConventional Controls Should Work

Exhaust Ventilation

Capture

InertiaDominants

DiffusionDominates

NoCapture

Air Stream

About1 nm

MostFine

Dusts

MicroScale

200 to300 nm

Approaches to Safe Nanotechnology in Research and Manufacturing

Engineering controls:

• Total enclosure of the process

• Partial enclosure with local exhaust ventilation

• Local exhaust ventilation

• General ventilation

http://www.cdc.gov/niosh/topics/nanotech/safenano/

Education and Training

Recommendations from NIOSHSummary of issuesApproaches to considerBasic GuidanceUpdated as new information comes on-

lineInput requested

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

Research progress in 10 key areasContinuing project plansOpportunities for collaboration

Information resources

Informational brochure seriesAvailable in large quantitiesUseful for communication of issues

What we know:• Some potential hazard

• Some exposure occurs

• Some risk may exist

• Nanoparticles can be measured

• Nanoparticles can be controlled

• Filters and respirators should protect

• There are no specific exposure limits

• There is no recommended medical surveillance guidance

• Nature and extent of hazard

• Nature and extent of exposure

• Nature and extent of risk

• What measures to use• Limitations of controls• Limitations of protection

• What limits are appropriate

• Content of medical surveillance

What we don’t know:

How to meet the challenge?

Collaboration!

•Share knowledge•Use expertise•Build experience•Partner

Thank you!

Charles.Geraci@cdc.hhs.gov