Nanosafety Manual

June 4, 2014

Nanomaterials Safety Manual

1. Asmatulu, F. Plummer and G. Miller Wichita State University

   Department of Environmental Health and Safety Wichita, KS 67260

    

   Safety and Environmental considerations are important part of our daily lives, not only for our individual protection, but for the protection of others and the environment as well. In order to maintain a high level of knowledge and responsiveness, each employee and faculty member is issued a copy of this manual. This safety manual is the guiding document of the University Safety Program. Each employee, student and faculty member is responsible for following/obeying to the rules included herein. Student workers are especially subject to accidents and environmental mistakes, and must be trained and guided by knowledgeable faculty and staff. Questions about the content of the manual should be directed to your supervisor or Environmental Health and Safety representatives.

   This informational booklet is proposed to provide a general overview of a particular safety related topic. This publication does not itself alter compliance responsibilities, which are set forth in OSHA standards themselves, Department of Environmental Health and Safety at Wichita State University.

    

   Table of Contents

   Page

    

   Table of Contents

   1. Introduction 3

   2. Nanoparticle Types 3

      1. Naturally Occurring 3

      2. Incidental Nanoparticles 3

      3. Engineered Nanoparticles 4

         1. Dimensions 4

         2. Morphology 4

         3. Phase Compositions 4

         4. Nanoparticle Uniformity and Agglomeration 5

   3. Nanoproducts 6

   4. Mechanisms Behind Toxicity of Nanomaterials 6

      1. Surface Chemistry 6

      2. Particle Size 6

      3. Surface Charges 6

      4. Surface Area 7

   5. Exposure Factors 7

      1. Concentration 7

      2. Duration 7

      3. Frequency 8

   6. Nanoparticle Hazards 8

      1. Inhalation Hazards 8

      2. Dermal Hazards 8

      3. Ingestion Hazards 8

   7. Best Practices for Handling Nanomaterials in Laboratories 9

      1. Preplan Ahead of Time 9

      2. Defining Toxicity of Nanoparticles 10

      3. Use Risk Assessment 10

      4. Exposure and Safety Assessment 12

      5. Prevent Inhalation Exposure during All Handling of Nanomaterials 12

      6. Work Practice Controls (Administrative Control) 13

      7. Personal Protective Equipment (PPE) 13

      8. Prevent Dermal Exposure to Nanomaterials (PPE-Gloves) 14

      9. Transportation and Labeling Requirements 14

      10. Fire and Explosion Hazards 15

      11. Prevent Contamination of Laboratory Surfaces 15

      12. Spill Cleanup 15

      13. Waste Handling 16

      14. Exposure Monitoring 16

   8. Summary 17

Definitions 18

References 22

Appendix 24

1. Introduction

   Nanotechnology is the manipulation of matter at an atomic, molecular, and/or supramolecular scale. Nanotechnology as the manipulation of matter with at least one dimension sized from 1 to 100 nanometers (1 nm = 10 Angstrom). At these length scales, materials begin to exhibit unique physical, chemical, physicochemical and biological properties that affect overall behavior of the materials.

    

   

   Source: http://networksandservers.blogspot.com/2011/01/nanotechnology.html

   Figure 1: A diagram showing various microscopic organisms in nanoscales and a list of nanodevices.

    

   Nanomaterials are increasingly used in a wide range of applications in science, technology, and medicine. The rapid development of a multitude of nanoparticle applications without clear guidelines necessitates assessing possible implications, assuring safe and sustainable handling of nanoparticles [1].

    

2. Nanoparticle Types

   Nanoparticles fall into three major types: naturally occurring, incidental, engineered [2].

    

   1. Naturally Occurring

      Examples of naturally occurring nanoparticles include; sea spray, mineral composites, volcanic ash, viruses [2].

   2. Incidental Nanoparticles

      A result of man-made industrial processes may cause some diseases.

      Table 1: Possible health effects cause by incidental nanoparticles [2]

      Incidental nanoparticles	Possible health effects
      Cooking smoke	Pneumonia, chronic respiratory disease and even lung cancer.
      Diesel exhaust	Cancer and respiratory disease.
      Welding fumes	Metal fume fever, infertility, benign pneumoconiosis.
      Industrial effluents	Asthma, atherosclerosis, chronic obstructive pulmonary disease.
      Sandblasting	Silicosis

   3. Engineered Nanoparticles

      Engineered nanoparticles comprise of any manufactured particles with nanoscale dimensions. Examples include; metals, quantum dots, buckyballs/nanotubes, sunscreen pigments, nanocapsules [2].

      1. Dimensions

          

         As shape, or morphology, of nanoparticles plays an important role in their toxicity, it is useful to classify them based on their number of dimensions. This is a generalization of the concept of aspect ratio [1]. Classification is based on the number of dimensions, which are not confined to the nanoscale range (<100 nm).

         1D nanomaterials: Materials with one dimension in the nanometer scale are typically thin films, coatings, multilayer, etc.

         2D nanomaterials: Two-dimensional nanomaterials have two dimensions in the nanometer scale. These include Tubes, fibers, wires, platelets, etc

         3D nanomaterials: Materials that are nanoscaled in all three dimensions are considered 3D nanomaterials. These include particles, quantum dots, hollow spheres, etc.

          

      2. Morphology

          

         Morphological characteristics to be taken into account are: flatness, sphericity, and aspect ratio. A general classification exists between high- and low-aspect ratio particles (Figure 2). High aspect ratio nanoparticles include nanotubes and nanowires, with various shapes, such as helices, zigzags, belts, or perhaps nanowires with diameter that varies with length. Small-aspect ratio morphologies include spherical, oval, cubic, prism, helical, or pillar. Collections of many particles exist as powders, suspension, or colloids.

      3. Phase Compositions

          

         Nanoparticles can be composed of a single constituent material or be a composite of several materials.

         Table 2: The phase compositions of nanoparticles

         Phase compositions	Examples
         Single-phase solids	Crystalline, amorphous particles and layers, etc.
         Multi-phase solids	Matrix composites, coated particles, etc.
         Multi-phase systems	Colloids, aerogels, ferrofluids, etc.

          

      4. Nanoparticle Uniformity and Agglomeration

          

         Based on their chemistry and electro-magnetic properties, nanoparticles can exist as dispersed aerosols, as suspensions/colloids, or in an agglomerate state (Figure 2). For example, magnetic nanoparticles tend to cluster, forming an agglomerate state, unless their surfaces are coated with a non-magnetic material. In an agglomerate state, nanoparticles may behave as larger particles, depending on the size of the agglomerate. Hence, it is evident that nanoparticle agglomeration, size and surface reactivity, along with shape and size, must be taken into account when deciding considering health and environmental regulation of new materials[2].

          

          

         

          

         Figure 2: Classification of nanostructured materials [2].

          

3. Nanoproducts

    

   Woodrow Wilson Center�s Project on Emerging Nanotechnologies (PEN) is a foundation which analyzes the nano consumer products. The PEN�s Consumer Products Inventory (CPI) contains a relatively large and complete nanoproduct list. As of October 2013, the nanotechnology consumer products inventory contains 1628 products or product lines.

   The consumer products have a wide range of applications, such as clothing, sports goods, personal care products, medicine, as well as contributing to faster and stronger cars and planes, more powerful computers and satellites, better micro and nanochips, and long-lasting batteries [3].

   Exposing nanomaterials may occur during the production, experimenting, transortion and also using nanoproducts. An example of exposure by nanoproduct usage includes aerosol sprays, sunscreen body lotion or taking supplements which contains nanomaterials.

    

4. Mechanisms Behind Toxicity of Nanomaterials

    

   1. Surface Chemistry

      A small aggregate or single particle is presumed to be more toxic than an aggregate of nanosized particle as the relative surface area could change, determining whether the material has a good wetting characteristic or has a surface characteristic that catalyzes specific chemical reactions or remains passive and allows fibrous tissue to grow on its surface.

   2. Particle Size

      A reduction in the size of nano-sized particles increases the particle surface area. Additional chemical molecules may attach to this surface, enhancing the reactivity and increasing toxic effects. Small nanoparticles (<100 nm) cause adverse respiratory health effects, typically causing more inflammation than larger particles made from the same material [2].

   3. Surface Charges

      High surface charge densities may cause higher cytotoxic effects than those with low charge densities. High surface charges react more intensely with cell membranes, creating additional damage to the cell [2].

      As an electrostatic property, Zeta potential measures the colloidal stability of nanomaterial samples in suspension. This is closely related to the particle surface charge and will heavily influence aggregation state. Through a low zeta potential colloids will tend to aggregate. The

      resulting aggregation may be observed through particle size and concentration measurements due to the increased size of aggregates, and the reduction in concentration of individual primary particles through aggregation [4].

   4. Surface Area

       

      Compared to micro particles, nanoparticles have a very large surface area and high particle number per unit mass. As the material in nanoparticulate form presents a much larger surface area for chemical reactions, reactivity is enhanced. According to Driscoll, 1996 and Oberd�rster, 2001, surface area is the metric that is highly correlated with particles induced adverse health effects [5].

      Oxidative stress: Most of the nanoparticles produce free radicals which cause oxidative stress. Biological oxidative stress may cause inflammation, cell destruction, and genotoxicity. The particle surface of the free radicals can activate the redox cycle and cause particle toxicity.

      As a particle size decreases the proportion of constituent atoms or molecules displayed on the surface increases. This increasing proportion of surface molecules represents the specific surface area of a particle. Through an increasing specific surface area the proportion of constituent molecules able to interact with the surrounding environment also increases. This represents an increased opportunity for chemical reactivity of a particle and therefore the production of Reactive Oxygen Species (ROS) and free radicals. ROS induced oxidative stress has been indicated as the underlying mechanism of nanomaterial toxicity with the potential to cause DNA damage, cytotoxicity, cell membrane disruption and interfere with cell signalling.

      ROS has also been indicated in secondary toxic effects of nanomaterials including oxidation of proteins and release of hazardous constituents [4].

       

5. Exposure Factors

   1. Concentration

       

      Small concentrations of nanoparticles with size smaller than 100 nm can have a higher probability of translocating to the circulatory system and organs (and produce damage) than high concentrations of the same particles. The measure that correlates with the effects is the surface area and not the mass dose.

   2. Duration

       

      High concentrations over a long duration are more likely to produce adverse health effects than the same or lower concentration over a shorter exposure period. Patients who have higher concentrations and longer durations of exposure result in greater doses to the victim and will more likely have harmful effects [6].

   3. Frequency

       

      The frequency of the exposure affects the concentration at the target site�can build up to a steady level-why some medications are taken three times a day vs. once a day to give the wanted effect [7].

       

6. Nanoparticle Hazards

    

   Adverse effects of nanoparticles on human health depend on individual factors such as genetics and existing disease, as well as exposure, and nanoparticle chemistry, size, shape, agglomeration state, and electromagnetic properties. The key to understanding the toxicity of nanoparticles is that their minute sizes are smaller than cells and cellular organelles, which allows them to penetrate these basic biological structures, disrupting their normal functions [1].

    

   Nanoparticle exposure during manufacturing and use may occur through:

    

   • Inhalation

   • Dermal

   • Ingestion

    

   1. Inhalation Hazards

       

      Inhalation of airborne nanoparticles may be deposited in the respiratory tract and also enter the blood stream and translocate to other organs. Some nanoparticles can induce cancers, including mesothelioma and also may cause rapid and persistent pulmonary fibrosis, cardiovascular dysfunction, and can migrate along the olfactory nerve into the brain [2].

       

   2. Dermal Hazards

       

      Human skin is composed of three distinct layers: the epidermis, dermis, and fat layer. Several studies indicated as a result of the thick skin layers, nanoparticles show little to no penetration of nanoscale oxides. However, various nanoparticles have been shown to affect the dermal:

       

      • Metal nanoparticles have been shown to penetrate damaged or diseased skin.

      • Iron oxide, nanotubes, TiO2, and silver have been shown to inhibit cell proliferation.

      • Nanotubes affect cell morphology.

      • Fullerenes damage cell membrane.

       

   3. Ingestion Hazards

       

      Ingestion occurs after inhalation exposure when mucus is brought up the respiratory tract and swallowed. Ingested nanoparticles may travel to other organ systems (e.g. liver, brain, and heart).

       

      Various hazard data show that ingestion of nanoparticles can cause adverse health effects:

      • Ingestion of colloidal silver can result in permanent discoloration of skin, nails and eyes.

      • Ingestion of Zinc Oxide can damage DNA of human intestinal cells.

         

        Control measures must be assessed for labs that use nanomaterial. Monitoring particle distribution in the work and laboratory areas is encouraged. Furthermore, biological monitoring measures:

         

      • Contaminants

      • Metabolites or enzymes in the blood

      • Urine

      • Exhaled breath

       

      

       

      Figure 3: Diseases associated to nanoparticle exposure [1].

       

7. Best Practices for Handling Nanomaterials in Laboratories

   1. Preplan Ahead of Time

       

      Preplan the experiments and determine equipment and procedures needed to factor in all the items discussed below.

      • These include equipment and procedures to prevent inhalation, skin or ingestion exposures, to prevent laboratory contamination, and to properly dispose of all nanomaterial waste.

      • Have appropriate spill materials on hand before beginning your work.

      • Equipment setup may require additional exhaust ventilation and installation or the use of respirators. All additions to or changes in exhaust ventilation must be approved by the EHS Office. All users of respirators must be fit tested to insure they are wearing the proper size. Contact the EHS Office for ventilation changes and respirator fit testing.

         

   2. Defining Toxicity of Nanoparticles

       

      • Be aware that many Safety Data Sheets (SDSs) currently shipped with nanomaterials refer to the bulk material toxicity information, which is inappropriate for the nanomaterial. Consider, but do not unquestioningly rely on, chemical hazard information for bulk/raw materials when developing controls for nanomaterials and any new information specific to the material at the scale being used [8-10].

      • If no information is available for your materials or the toxicity information is limited or uncertain, handle the material as if it is toxic.

      • The best place to keep up to date is the International Council on Nanomaterials (ICON) database which collects toxicity and environmental information by nanoparticle type (link is available on http://icon.rice.edu/report.cfm). Searches can be run on a specific nanomaterial for a particular time period, so only the most recent references are searched. You can also search Pub Med but the search results will be much broader than ICON [8].

         

   3. Use Risk Assessment

       

      Risk assessment is the determination of quantitative or qualitative value of risk related to an actual situation

      • Base your risk assessment on the type of nanomaterial (composition, shape, size, surface area, physical status) [9].

      • The Nanomaterial Risk Level (NRL) summary chart (Table 3) is a helpful tool to use for your initial risk assessment.

      • Reference Safety Data Sheet (SDS).

      • Utilize the proper engineering controls.

      • Utilize personal protective equipment (PPE).

      • Institute work practice controls (Administrative Control).

      • Contact EHS if assistance is needed

        Table 3: Summary of Recommended Nanomaterial Risk Levels (NRL) [8]

        Summary of Recommended Nanomaterial Risk Levels (NRL)
        NRL	Type of Nanomaterial