Aerosol Generation and Characterisation for Nanotoxicology

Transcription

1 Aerosol Generation and Characterisation for Nanotoxicology Alison Buckley Airborne Radioactivity Monitoring Users Group Meeting, NPL, Teddington 16 th November 2011

2 Introduction HPA Role The Health Protection Agency is an independent UK organisation set up by the government to protect the public from threats to their health from infectious diseases and environmental hazards. It does this by providing advice and information to national and local government, health professionals and the general public. The Agency's advice, information and services are underpinned by evidence-based research.

3 Introduction HPA Organisation Centre For Infections Communicable disease surveillance and specialist microbiology Centre for Emergency Preparedness and Response Applied microbiological research and emergency response The National Institute of Biological Standards and Control Standardisation and control of biological medicines, e.g. vaccines The Centre for Radiation, Chemical and Environmental Hazards

4 Introduction HPA Organisation

5 Introduction Nanotechnology and Nanotoxicology Rapid developments in the field of nanotechnology, have raised concerns over the potential impact on health Exposure to nanomaterials could occur during development, manufacture, use, or following disposal via inhalation, ingestion or dermal absorption Research into the risks associated with nanomaterials has lead to the development of a specialized branch of toxicology - Nanotoxicology Photo: topnews.in Informed by research on air pollution (ultrafine particles) and lessons learned from asbestos

6 Introduction Research Priorities in UK Nanotechnologies Strategy Inhalation; Ingestion; Dermal uptake; Transplacental movement In vitrostudies Interaction of NPs with cells and surface fluids at sites of entry (epidermal/lung/gut epithelium, endothelial cells of capillaries), dispersion across tissue barriers, effects on cells following uptake of NPs, mutagenicity, carcinogenicity. In vivostudies Toxicokinetics (dispersion, storage, excretion), dispersion across blood-brain and placental barriers, mutagenicitystudies, reproductive toxicity studies, volunteer studies e.g. intrapulmonary inflammatory responses. Priority nanomaterials High Aspect Ratio Nanoparticles (HARNs), Nanosilver, Metal Oxides

7 Introduction HPA and Nanotechnology Role to advise on the potential hazards and risks to human health associated with exposure to nanomaterials Responded to the challenge of the health concerns and knowledge gaps associated with nanomaterials by establishing the HPA NanotoxicologyResearch Centre >>To develop facilities and expertise to undertake a wide range of in vitro and in vivo studies, supporting experimental work and modelling studies

8 Introduction Key Work Areas Inhalation Studies Including toxico-kinetics, toxicology and heart-rate variability studies Dermal Nanotoxicology Development of flexing diffusion cell model to investigate skin penetration In vitro Studies Bioassays, genomics, cellular uptake

9 Introduction Key Work Areas Investigation of the effect of particle size on the toxico-kinetics of inhaled nanoparticles using spark generator produced aerosols of radioactive Iridium-192

10 Inhalation Studies Facility Requirements Developed an aerosol generation, characterisation and exposure system, designed specifically for nanomaterials and the challenges they present! Key Requirements: Controllable, reproducible and stable aerosol High number concentration Real-time aerosol characterisation Minimised risk of exposure to nanoparticles and radiation

11 Aerosol Generation Iridium nanoparticle aerosol produced using a PALAS spark generator To system Using neutron activated iridium electrodes a radioactive 192 Ir aerosol is produced Aerosol immediately diluted with oxygen and nitrogen and charge neutralised Optional humidifier All gas flows controlled by MFCs

12 Aerosol Generation Iridium nanoparticle aerosol produced using a PALAS spark generator 20 nm Using neutron activated iridium electrodes a radioactive 192 Ir aerosol is produced Aerosol immediately diluted with oxygen and nitrogen and charge neutralised Optional humidifier All gas flows controlled by MFCs 80 nm

13 Aerosol Generation Advantages: Radiolabel strongly bound Highaerosol number concentration Stable and reproducible aerosol production Size can be varied by changing the sparking frequency

14 Aerosol Generation Why Iridium? Beta and gamma emitter Half-life ~74 days Easily traceable for up to 6 months Not considered to be chemically toxic Low solubility Other Materials Gold, Silver, Titanium

15 Aerosol Characterisation >> Real-time measurement of key physical properties From generator >> Sampling for offline morphological and chemical analysis To extract

16 Characterisation of Administered Aerosol Size Distribution Size determines transport through and deposition site in the respiratory tract Size may affect translocation in the body Toxicological studies indicate that smaller particles may be more toxic than larger particles of the same material Number Concentration Toxicity studies indicate number concentration may correlate with biological effects Online monitoring allows any temporal changes in the exposure concentration to be tracked Mass Concentration Allows comparisonwith standard toxicology studies Combined with size measurements can give indication of surface area and density On-line: SMPS/APS CPC TEOM Off-line: EM EM Filtersampling (gravimetric analysis and activity counting) Surface Area Smaller particles have a larger total surface area per unit mass Toxicity studies have indicated acorrelation between surface area and biological effects, for a defined mass Derived from size and mass BET absorption measurement

17 Desirable Physical and Chemical Properties What does the material look like? Particle size/size distribution Agglomeration state/aggregation Shape Aspect ratio (for HARN) Surface morphology/topography Crystal structure Defect structure Porosity Surface area Solubility What is the material made of? Bulk elemental/molecular composition Purity Surface composition Surface charge (zeta potential)

18 Properties and Measurement Techniques Taken from ENRHES Report, available from: NPL Management Ltd - Internal

19 Aerosol Based Characterisation Techniques -Agglomerates Nanoparticles are often aggregate/agglomerates Size cannot be defined by a diameter alone Need to consider shape parameters such as fractal dimension and the size and number of primary particles Cannot assume a spherical model to determine mass, volume and surface area Need to consider what is the biologically relevant surface area

20 Approach to Health and Safety Nanomaterials No exposure limits specific to engineered nanomaterials Advice currently suggests a precautionary approach should be taken to risk management Approach to Health and Safety Involvement of Health and Safety Advisor (from earliest stage, part of project team) Health and Safety Plan developed and monitored Top risks identified Control measures identified Wherever possible used hierarchy of control principles

21 Particle Exposure Controls Workplace Ventilation Glove boxes LEV HEPA filtration PPE

22 Particle Exposure Monitoring General Direct measurement of airborne particulates SMPS, APS Radioactive NP Air sampling and counting Key issues: background and identification

23 Radiation Exposure Controls Electrodes Electrodes shielded with 10 cm thick lead Procedure developed for electrode handling and mounting Deposited particles Mass/activity deposited throughout the system estimated from theory and measurement Lead shielding installed at expected hotspots Regular monitoring will take place

24 Summary HPA role to advise on the potential hazards and risks to human health associated with exposure to nanomaterials HPA programmeto develop experimental facilities and expertiseto research the potential public health impact of exposures to nanomaterials The main initial focus of the programme is onthe inhalation exposure pathway

25 Summary Aerosol generation, characterisation and exposure facility developed, designed specifically for nanomaterials and the challenges they present Experiments planned using Spark Generated 192 Ir nanoparticles to investigate the effect of NP size on toxicokinetics Real-time characterisation of key physical parameters as well as sampling for additional offline chemical and morphological analysis Health and Safety considered at all stages