Respiratory Protection against Emerging Hazards Nanotechnology and H

Respiratory Protection against Emerging Hazards: Nanotechnology and H 1 N 1 Influenza A Virus Ron Shaffer Centers for Disease Control and Prevention National Institute for Occupational Safety and Health National Personal Protective Technology Lab Research Branch Pittsburgh, PA 15236 Email: RShaffer@cdc. gov Phone: 412 -386 -4001 October 2 nd, 2009 UC PRP Symposium October 2 2009

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: H 1 N 1 Pandemic Influenza - Can disposable filtering facepiece respirators (FFRs) be decontaminated and possibly reused? NPPTL Year Month Day Initials BRANCH

Occupational Safety & Health Act (1970) established OSHA & NIOSH - To assure safe and healthful working conditions for all working men and women. Regulation/Enforcement Research, Training, and Prevention Recommendations Department of Labor (DOL) Department of Health and Human Services (DHHS) Mine Safety and Health Administration (MSHA) Occupational Safety and Health Administration (OSHA) Centers for Disease Control and Prevention (CDC) National Institute for Occupational Safety and Health (NIOSH) NPPTL Year Month Day Initials BRANCH

42 CFR, Part 84 Air-purifying Particulate Respirator (APR) Certification Minimum Efficiency Na. Cl Test DOP oil Test 95% N 95 R 95 P 95 99% N 99 R 99 P 99 99. 97% N 100 R 100 P 100 • 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 NPPTL Year Month Day Initials BRANCH

Filtering Facepiece Respirators (FFR) · N 95 and P 100 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 NPPTL Year Month Day Initials BRANCH

Elastomeric Half Mask Respirator · N 95 and P 100 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 NPPTL Year Month Day Initials BRANCH

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/Nanoparticle. Final. Report 041006. pdf NPPTL Year Month Day Initials BRANCH

Conventional Single-Fiber Filtration Theory NPPTL Year Month Day Initials BRANCH

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 H 1 N 1 influenza A) NPPTL Year Month Day Initials BRANCH

Nanotechnology

What are Nanoparticles? Nanoparticles are particles having a diameter between 1 and 100 nm (0. 001 -0. 1 µm) Nanoparticles 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. NPPTL Year Month Day Initials BRANCH

Components of a Nanomaterial Risk Management Program · Hazard Determination · Process Review · Exposure Evaluation · Risk Characterization · Controls Adapted from Figure 1, Schulte et al, Occupational Risk Management of Engineered Nanoparticles, Journal of Occupational and Environmental Hygiene, 5: 4, 239 -249 (2008). Hierarchy of Controls Elimination/Substitution Engineering Controls Administrative Controls PPE NPPTL Year Month Day Initials BRANCH

Effectiveness of APR for Workers Handling Unbound Nanomaterials · 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? Photo obtained from Health hazard evaluation report: HETA-2005 -0291 -3025, Methner-MM; Birch -ME; Evans-D; Hoover-MD NPPTL Year Month Day Initials BRANCH

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 Porta. Count® with N 95 Companion™ measures ~40 nm particles · NIOSH is conducting controlled laboratory studies using manikins to measure face seal leakage of 5 – 400 nm particles NPPTL Year Month Day Initials BRANCH

Filtration of Nanoparticles – New Concerns? ? ? NPPTL Year Month Day Initials BRANCH

Filtration Performance of a Typical NIOSHApproved N 95 Filtering Facepiece Respirator n = 5; error bars represent standard deviations Sodium Chloride (TSI 3160); Silver (custom-built) Flow rate 85 L/min Filtration performance of NIOSH-approved N 95 and P 100 filtering facepiece respirators against nanoparticles, [2008] S. Rengasamy, WP King, B. Eimer and R. Shaffer, Journal of Occupational and Environmental Hygiene, 5: 556 -564. NPPTL Year Month Day Initials BRANCH

Summary : Percentage Penetration Results Approval Type Polydisperse Monodisperse Aerosol Test (MAT) (%) Aerosol Test (PAT) (%) (40 nm) (300 nm) NIOSH N 95 0. 61 - 1. 24 2. 0 - 5. 2 0. 20 - 1. 56 NIOSH P 100 0. 003 - 0. 022 0. 007 -0. 009 0. 0006 0. 001 CE FFP 2 0. 27 - 0. 50 1. 45 - 2. 22 0. 69 - 0. 84 CE FFP 3 0. 009 - 0. 014 0. 155 - 0. 164 0. 06 - 0. 07 FDA Surgical Mask 1. 58 - 88. 06 8. 98 - 72. 51 2. 14 - 88. 95 N/A Dust Mask 1. 00 - 87. 02 4. 31 - 81. 63 0. 86 - 95. 05 NPPTL Year Month Day Initials BRANCH

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). NPPTL Year Month Day Initials BRANCH

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 NPPTL Year Month Day Initials BRANCH

Where to learn more Visit the NIOSH Nanotechnology Topic Page http: //www. cdc. gov/niosh/topics/nanotech/ NPPTL Year Month Day Initials BRANCH

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 rankordering 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) NPPTL Year Month Day Initials BRANCH

Recent Papers · Rengasamy S, Verbofsky R, King WP and Shaffer RE, Nanoparticle penetration through NIOSH-approved N 95 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 N 95 and P 100 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). NPPTL Year Month Day Initials BRANCH

2009 H 1 N 1 Flu

Background – 2006 IOM Report · >90 million N 95 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 NPPTL Year Month Day Initials BRANCH

Reusability of Filtering Facepiece Respirators 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 project Note: 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. NPPTL Year Month Day Initials BRANCH

Task 1. Effect of Decontamination on Filtration · Experimental Design - 1 N 95 and 1 P 100 FFR model - Automated systems: autoclave, VHP, Et. O - 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, Et. O, 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 change Viscusi 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. NPPTL Year Month Day Initials BRANCH

Effect of Decontamination on Physical Appearance, Odor, and Laboratory Performance · Experimental Design - 3 N 95, 3 Surgical N 95, 3 P 100 FFRs - Bleach, UV, VHP, Et. O, and Microwave · 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 (P 100) and material near metal nose clip (Surgical N 95) 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 Viscusi DJ, Bergman, M. S. , Eimer, B. C. , and Shaffer RE. Evaluation of Five Decontamination Methods for Filtering Facepiece Respirators. chlorine gas were found after rehydration Annals of Occupational Hygiene (in press). NPPTL Year Month Day Initials BRANCH

N 95 FFR average initial sodium chloride filter aerosol penetration versus temperature Five SN 95 -D FFRs melted: one at 100 C, two at 110 C, and two at 120 C NPPTL Year Month Day Initials BRANCH

Modes of Contamination Infected Person Respirator User · Sneezing · Droplets (~0. 5 - 10+ µm) · Coughing · Droplet nuclei (~0. 3 - <5 µm) · Breathing · Talking NPPTL Year Month Day Initials BRANCH

Visual Differences in Aerosol and Pipette Loading Methods Microphotographs of the FFR Loaded with Aerosol to 1 E+05 pfu/cm 2 (Left: Outer Layer and Right: Media Layer) 10 µm Microphotographs of the FFR Loaded with Liquid Droplets 10 µm (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 NPPTL Year Month Day Initials BRANCH

Bio-Aerosol Respirator Test System (BARTS) Schematic 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 holders 11. Flow meter 12. Vacuum pump 13. Timer 14. Power 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) NPPTL Year Month Day Initials BRANCH

BARTS Validation Combined APS & SMPS Data · Size distribution of MS 2 aerosol challenge highly dependent upon concentration of protective factor NPPTL Year Month Day Initials BRANCH

BARTS Validation · Some virus-containing droplet nuclei penetrate through the filter layers – distribution through the FFR is highly dependent upon concentration of protective factor NPPTL Year Month Day Initials BRANCH

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 MS 2 viral aerosol challenge reduced decontamination efficacy for bleach, but not MGS NPPTL Year Month Day Initials BRANCH

Droplet Phase Aerosol Respirator Test System (DPARTS) Schematic Challenge Aerosol 1. compressed air supply FFR 6. 2. HEPA filter 6 B. FFR sample coupons on 3. air flow regulator the respirator 4. nebulizer air inlet 7. exhaust port with HEPA 5. nebulizer filter; 8. aerodynamic particle sizer 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). NPPTL Year Month Day Initials BRANCH

Example Applications of DPARTS Bleach UV · Decontamination efficacy increases as a function of dose NPPTL Year Month Day Initials BRANCH

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 MS 2 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 MS 2 particles to acceptable levels (with or without a cleaning step)? - Does decontamination change FFR fit? NPPTL Year Month Day Initials BRANCH

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) NPPTL Year Month Day Initials BRANCH

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 · Do. D (TSWG) for continued support of the FFR reuse study (multiple decontaminations, fit testing study). Air Force Research Laboratory for providing the H 1 N 1 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 NPPTL Year Month Day Initials BRANCH

Quality Partnerships Enhance Worker Safety & Health 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. Thank you NPPTL Year Month Day Initials BRANCH

Extra Slides NPPTL Year Month Day Initials BRANCH

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/ NPPTL Year Month Day Initials BRANCH

Primary Decontamination Methods TSWG Funded Collaboration UV-C Light 254 nm at 2. 0 m. W/cm 2 for 15 min each side Microwave Generated Steam 2 min on ‘High’ power (2 pipette-tip boxes each with 50 ml tap water) Moist Heat Incubator (60°C, 80% RH) for 30 min NPPTL Year Month Day Initials BRANCH

Quick Comparison of the Systems · BARTS · DPARTS - Droplet Nuclei - Droplet - Coupons - Full FFR - Vacuum pulls challenge into media of the coupon - Direct spray onto the surface of the respirator - Simulate air circulating particles - 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) NPPTL Year Month Day Initials BRANCH

Aerosol Media used in BARTS Characterization and Validation · ATCC medium 271 - Growth medium for E. coli (used to propagate and enumerate MS 2) · 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 Glucose - . 01 1. 0 Calcium chloride - . 002 0. 22 Thiamine - . 0001 . 01 8. 5 * Constituents (g/L) NPPTL Year Month Day Initials BRANCH