Respiratory Protection against Emerging Hazards: Nanotechnology and H1N1 Influenza A Virus Centers for Disease Control and Prevention National Institute

Respiratory Protection against Emerging Hazards: Nanotechnology and H1N1

Influenza A Virus

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

National Personal Protective Technology LabResearch Branch

Pittsburgh, PA 15236Email: [email protected]

Phone: 412-386-4001

October 2nd, 2009

Ron Shaffer

UC PRP Symposium October 2 2009

NPPTL Year Month Day Initials BRANCH

Overview

Respirator 101: Air purifying respirators (APR)

Emerging Hazard: Engineered Nanoparticles

Do NIOSH-certified APRs provide expected levels of filtration performance against nanoparticles?

Emerging Hazard: H1N1 Pandemic Influenza

Can disposable filtering facepiece respirators (FFRs) be decontaminated and possibly reused?


Mine Safetyand Health

Administration(MSHA)

Department of Health and Human Services

(DHHS)

Department of Labor(DOL)

Regulation/Enforcement

OccupationalSafety and Health

Administration(OSHA)

Research, Training, andPrevention Recommendations

Centers for DiseaseControl and Prevention

(CDC)

National Institute forOccupational Safetyand Health (NIOSH)

Occupational Safety & Health Act (1970) established OSHA & NIOSH - To assure safe and healthful working conditions for all working men and women.


42 CFR, Part 84 Air-purifying Particulate Respirator (APR) Certification

Minimum Efficiency

NaCl Test

DOP oil Test

DOP oil Test

95% N95 R95 P95

99% N99 R99 P99

99.97% N100 R100 P100

• N - not resistant to oil mist• R - resistant to oil mist• P - protective against oil mist• 95, 99, 100 - minimum filter efficiency using certification test conditions


Filtering Facepiece Respirators (FFR)

N95 and P100 most common

Designed to form tight face seal

Entire facepiece is composed of the filtering medium

Approximate cost: $0.70 - $2.34 each

Mostly fixed-length straps

Disposable


Elastomeric Half Mask Respirator

N95 and P100 most common

Designed to fit tightly to the face

Low maintenance - reusable facepiece and replaceable filters and cartridges

User-adjustable-length straps

Approximate cost:

Facepiece: $12 to $35

Filters: $4 to $8 each


Example Electret Filter Media

Melt blown - Corona charged (A)

Melt blown - Highly charged (B)

Extruded - Split film fiber (C)

Melt blown - Highly charged (D)

http://www.cdc.gov/niosh/npptl/researchprojects/pdfs/NanoparticleFinalReport041006.pdf


Conventional Single-Fiber Filtration Theory


Current State of Respiratory Protection

Effectiveness of NIOSH-approved APRs against conventional workplace hazards has been shown

Workplace protection factor (WPF) studies

OSHA Assigned Protection Factors (APF)

Emerging hazards raise new issues:

Nanotechnology

Infectious aerosols (e.g., SARS, avian influenza, 2009 H1N1 influenza A)

Nanotechnology


What are Nanoparticles?

Nanoparticles are particles having a diameter between 1 and 100 nm (0.001-0.1 µm)

Adapted from: Guidance for Filtration and Air-Cleaning Systems to Protect Building Environments from Airborne Chemical, Biological, or Radiological Attacks, DHHS (NIOSH) Publication No. 2003-136.

Nanoparticles


Components of a Nanomaterial Risk Management Program

Adapted from Figure 1, Schulte et al, Occupational Risk Management of Engineered Nanoparticles, Journal of Occupational and Environmental Hygiene, 5:4, 239-249 (2008).

Hazard Determination

Process Review

Exposure Evaluation

Risk Characterization

Controls

Hierarchy of Controls

Elimination/Substitution

Engineering Controls

Administrative Controls

PPE


Effectiveness of APR for Workers Handling Unbound Nanomaterials

Photo obtained from Health hazard evaluation report: HETA-2005-0291-3025, Methner-MM;

Birch-ME; Evans-D; Hoover-MD

Effectiveness of particulate APR is primarily a function of leakage around the face seal and penetration through the filter.

Key question: Do nanoparticles behave any differently than larger particles?


Respirator Fit

No specific data available to determine if nanoparticle face seal leakage is different

WPF studies have validated efficacy of current methods used to fit respirators for protection against gases and vapors.

TSI PortaCount® with N95 Companion™ measures ~40 nm particles

NIOSH is conducting controlled laboratory studies using manikins to measure face seal leakage of 5 – 400 nm particles


Filtration of Nanoparticles – New Concerns?

?

?


Filtration Performance of a Typical NIOSH-Approved N95 Filtering Facepiece Respirator

n = 5; error bars represent standard deviationsSodium 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

enet

rati

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.


Summary : Percentage Penetration Results

Approval TypePolydisperse Aerosol Test

(PAT) (%)

Monodisperse Aerosol Test (MAT) (%)

(40 nm) (300 nm)

NIOSH N95 0.61 - 1.24 2.0 - 5.2 0.20 - 1.56

NIOSH P100 0.003 - 0.022 0.007-0.0090.0006 -

0.001

CE FFP2 0.27 - 0.50 1.45 - 2.22 0.69 - 0.84

CE FFP3 0.009 - 0.014 0.155 - 0.164 0.06 - 0.07

FDASurgicalMask 1.58 - 88.06 8.98 - 72.51 2.14 - 88.95

N/ADust Mask 1.00 - 87.02 4.31 - 81.63 0.86 - 95.05


Correlation of Poly- and 40 nm Monodisperse Aerosol Penetrations

Shaffer, RE, Rengasamy, S., Respiratory Protection Against Nanoparticles: A Review, Journal of Nanoparticle Research (in press, available on-line).


Where do we go from here?

PPE

Laboratory studies on efficacy of protective clothing and gloves; complete laboratory studies on respiratory protection

PPE workplace protection factor (field) studies of nanotechnology workers

Applications

Antimicrobial effects on HVAC air and respirator filters

Use of monolayer-protected gold nanoparticles in air purifying respirator end of service life indicators

http://www.cdc.gov/niosh/topics/nanotech/pdfs/NIOSH_Nanotech_Strategic_Plan.pdf


Where to learn more

Visit the NIOSH Nanotechnology Topic Page http://www.cdc.gov/niosh/topics/nanotech/


Summary

NIOSH has an active nanotechnology research program

For respirator filter media there is no deviation from the classical single-fiber theory for filtration of particulate as small as 4 nm in diameter

Polydisperse aerosol test provided a consistent rank-ordering of filtration performance seen with 40 nm (MPPS) monodisperse particles

It is likely that NIOSH approved APRs when used in a complete respirator program will be useful for protecting workers from nanoparticle inhalation and should provide levels of protection consistent with their OSHA assigned protection factor (APF)


Recent Papers

Rengasamy S, Verbofsky R, King WP and Shaffer RE, Nanoparticle penetration through NIOSH-approved N95 filtering facepiece respirators. Journal of the International Society for Respiratory Protection, 24(1):49-59 (2007).

Rengasamy, S., Eimer, B, Shaffer, RE, Nanoparticle filtration performance of commercially available dust masks, Journal of the International Society for Respiratory Protection, 25(1): 27-41 (2008).

Rengasamy, S., King, WP, Eimer, B, Shaffer, RE, Filtration performance of NIOSH-approved N95 and P100 filtering facepiece respirators against 4 to 30 nanometer size nanoparticles, Journal of Occupational and Environmental Hygiene, 5(9): 556-564 (2008).

Rengasamy A, Eimer BC, Shaffer RE, Comparison of nanoparticle filtration performance of NIOSH-approved and CE-marked particulate filtering facepiece respirators. Ann Occup Hyg 53(2): 117-128 (2009).

Rengasamy, S., Miller, A., Eimer, B, Shaffer, RE, Filtration Performance of FDA-approved Surgical Masks, Journal of the International Society for Respiratory Protection, 26(1):54-70 (2009).

Shaffer, RE, Rengasamy, S., Respiratory Protection Against Nanoparticles: A Review, Journal of Nanoparticle Research (in press, available on-line).

2009 H1N1 Flu


Background – 2006 IOM Report

>90 million N95 FFR will be needed to protect workers in the healthcare sector during a 42-day outbreak

Can disposable FFRs be reused?

Biological decontamination method must (1) remove the viral threat; (2) be harmless to the user; and (3) not compromise the integrity of the FFR.

Little data exists

http://www.nap.edu/catalog.php?record_id=11637


Reusability of Filtering Facepiece Respirators

Task 1: Effect of decon on FFR filter performance

Task 2: Develop STP for measuring the efficacy of

FFR decon

Task 3: Survivability of virus simulant on FFR

Task 4: Reaerosolization of virus on FFR

Task 5: Assessment of decon strategies for

FFR

Task 6: Effect of decon on FFR fit

Task 7: Final Report

Task 1: Effect of decon on FFR filter performance

Task 2: Develop STP for measuring the efficacy of

FFR decon

Task 3: Survivability of virus simulant on FFR

Task 4: Reaerosolization of virus on FFR

Task 5: Assessment of decon strategies for

FFR

Task 6: Effect of decon on FFR fit

Task 7: Final Report

Goal - conduct laboratory studies to understand the efficacy of decontamination and to assess the impact of decontamination on FFR performance

Note: Tasks 3 and 4 (not shown) are related to other aspects of the projectNote: This presentation only includes data from the NIOSH funded project. Data from our TSWG-funded collaboration with AFRL, FDA, University of Florida, and University of Nebraska is not included.


Task 1. Effect of Decontamination on Filtration

Experimental Design

1 N95 and 1 P100 FFR model

Automated systems: autoclave, VHP, EtO

Chemical: IPA, Bleach, LHP, Soap & Water

Physical: UV, microwave, heat

Controls: water, no decon

Findings

Autoclave, 160º C heat, 70% IPA, and soap & water caused significant filter degradation

Bleach, EtO, and a microwave degraded filter performance, but particle penetration levels were still less than the NIOSH certification criteria.

HP (vaporized and liquid forms) and UV radiation caused no significant changeViscusi DJ, King WP, Shaffer RE. Effect of Decontamination on the Filtration Efficiency of Two Filtering Facepiece Respirator Models. Journal of the International Society for Respiratory Protection, (2007) 24: 93-107.


Effect of Decontamination on Physical Appearance, Odor, and Laboratory Performance

Findings

Effects were model specific. FFRs tested have differences in their design (e.g., # of layers, face seal enhancements) and materials of construction (e.g., hydrophobicity)

Inner face seal liner (P100) and material near metal nose clip (Surgical N95) on two FFR models melted in microwave

All other combinations had expected levels of laboratory performance (filtration, air flow resistance)

Bleach has noticeable odor - even after drying 22 hours - and low levels of chlorine gas were found after rehydration

Experimental Design

3 N95, 3 Surgical N95, 3 P100 FFRs

Bleach, UV, VHP, EtO, and Microwave

Viscusi DJ, Bergman, M.S., Eimer, B.C., and Shaffer RE. Evaluation of Five Decontamination Methods for Filtering Facepiece Respirators. Annals of Occupational Hygiene (in press).


N95 FFR average initial sodium chloride filter aerosol penetration versus temperature

Five SN95-D FFRs melted: one at 100C, two at 110C, and two at 120C


Modes of Contamination

Respirator User

Infected Person

Sneezing

Coughing

Breathing

Talking

Droplets (~0.5 - 10+ µm)

Droplet nuclei (~0.3 - <5 µm)


Microphotographs of the FFR Loaded with Aerosol to 1E+05 pfu/cm2(Left: Outer Layer and Right: Media Layer)

10 µmMicrophotographs of the FFR Loaded with Liquid Droplets

(Left: Outer Layer and Right: Media Layer)

Aaron W. Richardson, Shannon D. Harpest, and Kent C. Hofacre, Reaerosolization of Viruses from NIOSH-certified Filtering Facepiece Respirators, Battelle Columbus Operations, Final Report to NIOSH on Contract No. 200-2000-08018

Visual Differences in Aerosol and Pipette Loading Methods

10 µm


Bio-Aerosol Respirator Test System (BARTS)

1. Air supply 2. Regulator 3. HEPA filter 4. Nebulizer air 5. Nebulizer 6. Dilution air 7. Chamber

8. Circulation fan 9. Exhaust port 10. Test holders11. Flow meter12. Vacuum pump13. Timer14. Power

1

2

25

6

3

7

8

12

13

14

4

3

14

11

11

3

93

10

10

Schematic

Photo

Fisher, E., Rengasamy, S., Viscusi, D., Vo, E., and Shaffer, R., Development of a Test System to Apply Virus-Containing Particles to Filtering Facepiece Respirators for the Evaluation of Decontamination Procedures, Applied and Environmental Microbiology, 75(6): 1500-1507 (2009)


BARTS ValidationCombined APS & SMPS Data

Size distribution of MS2 aerosol challenge highly dependent upon concentration of protective factor


BARTS Validation

Some virus-containing droplet nuclei penetrate through the filter layers – distribution through the FFR is highly dependent upon concentration of protective factor


Example Applications of BARTS

Bleach Microwave Generated Steam (MGS)

Decontamination efficacy increases as a function of dose and time

Increased organic load (protection factor) in the MS2 viral aerosol challenge reduced decontamination efficacy for bleach, but not MGS


Droplet Phase Aerosol Respirator Test System (DPARTS)

Schematic

Vo, E., Rengasamy, S., and Shaffer, R., Development of a Test System to Evaluate Decontamination Procedures for Viral Droplets on Respirators Applied and Environmental Microbiology, (in press).

Challenge Aerosol

T

C R

B

L

6B

APS1

3

5

4

7 2

2

6

8

1. compressed air supply 2. HEPA filter3. air flow regulator 4. nebulizer air inlet 5. nebulizer

6. FFR 6B. FFR sample coupons on the respirator7. exhaust port with HEPA filter; 8. aerodynamic particle sizer


Example Applications of DPARTS

Bleach UV

Decontamination efficacy increases as a function of dose


Summary

Some biological decontamination methods caused significant changes in physical appearance and/or degradation in laboratory performance. Some of these effects were model specific.

BARTS and DPARTS produce reproducible MS2 phage aerosol challenges for FFR decontamination efficacy studies

UV, microwave generated steam, and moist heat appear to be promising, but additional research is necessary:

Can the low-temperature biological decontamination methods reduce viable MS2 particles to acceptable levels (with or without a cleaning step)?

Does decontamination change FFR fit?


Respiratory Protection Research Needs

Aerosol/Filtration Studies

Antimicrobial

Respirator Fit Research

Facial anthropometrics

Fit Testing

Novel respirator designs

Influenza Pandemic

Assess strategies to prevent FFR shortage

Performance (laboratory & field)


Acknowledgements

NIOSH NTRC for funding a pilot study on nanoparticle filtration

CDC for initial funding on the development of BARTS and the FFR reuse study

DoD (TSWG) for continued support of the FFR reuse study (multiple decontaminations, fit testing study). Air Force Research Laboratory for providing the H1N1 decontamination data (not presented).

Respiratory Protection against Nanoparticle Team: Samy Rengasamy (PI), Ben Eimer, Bill King

FFR Reuse Team: Dennis Viscusi, Evanly Vo, Samy Rengasamy, Ed Fisher, Debbie Novak, Bill King, Mike Bergman


Quality Partnerships Enhance Worker Safety & Health

Thank you

Visit Us at: http://www.cdc.gov/niosh/npptl/Disclaimer:

The findings and conclusions in this presentation have not been formally disseminated by the National Institute for Occupational Safety and Health and should not be construed to represent any agency determination or policy.


Extra Slides


Nanoparticles - Health Concerns

Airborne nanomaterials can be inhaled and deposited in the respiratory tract

Nanomaterials can enter the blood stream and translocate to other organs

Mass doses of insoluble nanoparticles are more potent than larger particles of similar composition in causing pulmonary inflammation and lung tumors in laboratory animals

Changes in the chemical composition, structure of the molecules, or surface properties can influence potential toxicity http://www.cdc.gov/niosh/topics/nanotech/


Primary Decontamination MethodsTSWG Funded Collaboration

Microwave Generated Steam2 min on ‘High’ power (2 pipette-tip boxes each with 50 ml tap water)

Figure 12.2: Treatment of FFRs with 254 nm UV lightUV-C Light254 nm at 2.0 mW/cm2 for 15 min each side

Moist HeatIncubator (60°C, 80% RH) for 30 min


Quick Comparison of the Systems BARTS

Droplet Nuclei

Coupons

Vacuum pulls challenge into media of the coupon

Simulate air circulating particles

DPARTS

Droplet

Full FFR

Direct spray onto the surface of the respirator

Simulates direct particle deposition (sneeze or cough)

Fisher E., Rengasamy S., Viscusi D., Vo E., and R. Shaffer. 2009. Development of a Test System To Apply Virus-Containing Particles to Filtering Facepiece Respirators for the Evaluation of Decontamination Procedures. APPLIED AND ENVIRONMENTAL MICROBIOLOGY 75:1500–1507.

Vo E., Rengasamy S., and R. Shaffer. 2009. Development of a Test System to Evaluate Decontamination Procedures for Viral Droplets on Respirator Surfaces. APPLIED AND ENVIRONMENTAL MICROBIOLOGY (in press)


Aerosol Media used in BARTS Characterization and Validation

ATCC medium 271

Growth medium for E. coli (used to propagate and enumerate MS2)

Protective factor (organic challenge) in decontamination testing

High Protective Factor (HPF)

Low Protective Factor (LPF)

Follows the parameters set forth in ASTM E 1053 (Efficacy of Virucidal Agents Intended for Inanimate Environmental Surfaces)

ATCC 271 Water LPF (1%) * HPF (100%) * ASTM E 1053 *

Tryptone - .10 10.0 7.6

Yeast extract - .01 1.0

Sodium chloride - .08 8.0 8.5

Glucose - .01 1.0

Calcium chloride - .002 0.22

Thiamine - .0001 .01 * Constituents (g/L)

Documents

Respiratory Protection against Emerging Hazards: Nanotechnology and H1N1 Influenza A Virus Centers for Disease Control and Prevention National Institute