Arbocatalogus Nederlandse Universiteiten

2009-5062 ACNU GS GP5 Nanosafety guidelines.doc

Arbocatalogus Nederlandse Universiteiten

Onderwerp: Gevaarlijke stoffen

Good Practice #5 Nanosafety Guidelines - Recommendations for research activities with ‘free nanostructured matter’ within the Dutch Universities

Nanosafety Guidelines

Workgroup NanoSafety

& Authors: Dick Hoeneveld

Jelan Kuhn

John Nijenhuis

Roel Kamerling

Andreas Schmidt-Ott

Edited: John Nijenhuis & Valerie Butselaar-Orthlieb

Date: September 2008

Document version Version 1.3

Contact info: Delft University of Technology

Faculty of Applied Science

VGWM Committee of DelftChemTech

Valerie Butselaar-Orthlieb

Julianalaan 136

2628 BL Delft

The Netherlands

Scope: The present guidelines have been set up in view of research activities within Dutch Universities (VSNU). They refer to processes, where “free nanostructured matter”, i.e. particles in the form of aerosols, liquid suspensions or powders are produced, processed or handled in quantities that may be dangerous concerning health effects or explosion risks. The present document is meant to be updated periodically, taking into account new domains of research activities as well as the increasing knowledge on nanoparticle properties that present risks. In particular, the input of researchers working in the faculty will be incorporated in the update of these guidelines. The present recommendations have been kept very concise and readable for a maximum impact.

Contents

1. Introduction 4

2. Regulations and guidelines concerning nanoparticles presently available 5

3. Conclusions on nanosafety from the available literature 7

3.1 Toxicity 7

3.2 Pyrophoricity 9

4. Nanosafety recommendations 10

4.1 Handling of nanopowders 10

4.2 Handling of nanoparticle suspensions in liquids 10

4.3 Processing of nanoparticles in the gas phase: Gas Phase Nanoparticle Reactors 10

4.4 Continuous monitoring of the lab air 10

4.5 Cleaning of vessels and nanoparticle contaminated objects 11

4.6 Disposal of Nanoparticles 11

4.7 Transport 11

4.7 Summary 12

5. Literature 13

5.1 General, Safety Issues in Nanotechnology 13

5.2 Nanotoxicology 13

5.3 Particle Measurement 14

6. Acknowledgment 14

1. Introduction

Nanoparticles reveal interesting properties from a technological point of view, such as their high degree of reactivity and selectivity in catalytic reactions.

However, these specific properties could also make them hazardous to people and their environment. The current debate on the risks of nanotechnologies tends to focus on the potential dangers of nanoparticles. A growing interest for the production and application of nanoparticles has generated the need for appropriate safety measures.

Although there is no international definition, the general accepted description for a nanoparticle is: particles having one or more dimensions of the order of 100 nm or less’. Micro- and nanoparticles have always been part of our natural environment. But, over the centuries, their quantity in the air is increasing rapidly due to combustion of fossil fuels. It has been shown that high concentrations of fine dust particles in urban air can be harmful to human health.

Toxicological research has generated a great deal of information on the relationship between the physical and chemical properties of fine particles and their adverse effect on our health. The knowledge on these interactions is however far from complete.

The question facing scientists today is to what extent the current knowledge on ‘traditional’ fine particles is applicable to the new generation of nanoparticles. These synthetic nanoparticles include nanotubes, fullerenes, nanowires, quantum dots and particles used for drug delivery and diagnosis. Due to their odd shapes and high reactivity, their effect on the metabolism cannot easily be predicted.

Fine dust particles are known to penetrate deep into the lungs. Nanoparticles are even able to bypass and damage the clearing mechanism of the lungs. If they do not readily dissolve or break down, they will accumulate and cause more damage.

Because of the minute size of nanoparticles, they are able to enter cells and disrupt cellular metabolism. Their ability to cross barriers enables them to enter the circulation system via the lungs or even enter the brain via the nasal mucous membrane.

Inside the body, they can promote the formation of harmful substances such as reactive oxygen compounds. Additionally, they can evoke inflammatory reactions which eventually lead to harmful levels of reactive substances in the blood, derived from the immune system. It is believed that these mechanisms form the basis for the observed relationship between the presence of fine dust particles in the air and disorders in the respiratory and circulatory system in humans.

Less is known about the ability of nanoparticles to penetrate though the skin or digestive tract. Until more research on this subject has been done, care should be taken. At present time, there is little chance that the general public will be exposed to synthetic nanoparticles. The people most at risk are those who synthesize and work with these particles, in various research centres.

These guidelines were set-up to protect the people from the Dutch Universities from the potential hazards of the nanoparticles they are working with. The guidelines will be updated and sharpened, based on the latest developments in toxicological research on nanoparticles.

2. Regulations and guidelines concerning nanoparticles presently available

Currently there are no official regulations or guidelines concerning the safety and environmental implications of working with engineered nano particles. In response to the absence of a consolidated understanding of current health, environmental, and stewardship practices in nanomaterial manufacturing, the International Council on Nanotechnology (ICON) issued a request for proposals (RFP) in December 2005 for the performance of a survey of current practices. Numerous international organizations[1] are currently working on legislation and guidelines for nanomaterials. A document with descriptions of recommended “best practices” and frameworks (WK8985) is currently under development by ASTM international. This document will describe standards and guidance for health and safety in the nanotechnology industry. A committee of the `Health Council of the Netherlands has issued a monograph in English with the title “Health Significance of Nanotechnologies” in early 2007. Part of the present introduction is taken from that study. The committee states in its conclusions that “ … the toxicity of nanoparticles could differ qualitatively and quantitatively from the toxicity of the same material in the form of larger particles” and recommends, among others, that “synthetic free nanoparticles should be treated as new substances, even if the chemical composition is not new.” The study gives almost no specific advice in how to handle nanomaterials but mentions that another committee is presently dealing with such questions. This is exemplary for the present situation on an international level. In numerous discussions with colleagues from research institutes and a Workshop on Nanotoxicity (St. Paul, USA, Oct. 2006), one of the authors of the present recommendations (A.S.) learned that most labs with nanoparticle activities are thinking about setting up guidelines, but no example of such guidelines found satisfactory has been found worldwide.

The guidelines that have been issued by other institutions are quite generic. For example, Dr. P. Lichty of the Lawrence Berkely National Laboratory has set-up the following guidelines for working with nanomaterials.

· Use good general laboratory safety practices as found in your chemical hygiene plan. Wear gloves, lab coats, safety glasses, face shields, closed-toed shoes as needed.

· Be sure to consider the hazards of precursor materials in evaluating process hazards.

· Avoid skin contact with nanoparticles or nanoparticle-containing solutions by using appropriate personal protective equipment. Do not handle nanoparticles with your bare skin.

· If it is necessary to handle nanoparticle powders outside of a HEPA-filtered powered-exhaust laminar flow hood, wear appropriate respiratory protection. The appropriate respirator should be selected based on professional consultation.

· Use fume exhaust hoods to expel fumes from tube furnaces or chemical reaction vessels.

· Dispose of and transport waste nanoparticles according to hazardous chemical waste guidelines.

· Vacuum cleaners used to clean up nanoparticles should be tested, HEPA-filtered units.

· Equipment previously used to manufacture or handle nanoparticles should be evaluated for potential contamination prior to disposal or reuse for another purpose.

· Lab equipment and exhaust systems should also be evaluated prior to removal, remodeling, or repair.

· Given the differing synthetic methods and experimental goals, no blanket recommendation can be made regarding aerosol emissions controls. This should be evaluated on a case by case basis.

· Consideration should be given to the high reactivity of some nanopowder materials with regard to potential fire and explosion hazards.

On clean-up of nanomaterial spills, the NIOSH report ‘Approaches to Safe Nanotechnology” states that until relevant information is available, the strategies of cleaning up nano-spills should be based on existing regulations and good practice. Standard approaches to cleaning up powder and liquid spills include the use of HEPA-filtered vacuum cleaners, wetting powders down, using dampened cloths to wipe up powders and applying absorbent materials/liquid traps. When developing procedures for cleaning up nanomaterial spills, consideration should be given to the potential for exposure during cleanup. Inhalation exposure and dermal exposure will likely present the greatest risks. Consideration will therefore need to be given to appropriate levels of personal protective equipment. Inhalation exposure in particular will be influenced by the likelihood of material re-aerosolization. In this context, it is likely that a hierarchy of potential exposures will exist, with dusts presenting a greater inhalation exposure potential than liquids, and liquids in turn presenting a greater potential risk than encapsulated or immobilized nanomaterials and structures.

Concerning toner dust, the Platform Gezondheid en Milieu mentions that exposure to toner dust can cause irritation of the respiratory system and allergic reactions. However, these effects are rare and are mainly observed with people which were subjected to large amounts of toner dust. They recommend further research, and printers and copy machines to be placed in a separate, ventilated room. Achmea Arbo says the risks are minimal, as long as the existing guidelines are being followed.

3. Conclusions on nanosafety from the available literature

Health hazards in the present work of the universities are mainly limited to inhalation toxicity. The requirement of avoiding inhalation exposure automatically reduce exposure to the skin or the eyes, and hand contact in handling powders or suspensions can easily be avoided by wearing gloves[2].

A second safety hazard arises from the fact that nanoparticle powders are frequently pyrophoric, i.e. they self-ignite under exposure to air, even if the bulk material shows no such tendency. With samples exceeding the milligram range, precautions have to be taken.

3.1 Toxicity

From what is presently known particles must be considered as (potentially) toxic and hence treated as nanotoxic, if the following criteria are fulfilled:

- The macroscopic material is classified as toxic.

and/or

- The particles fulfil all of the following criteria:

o Their primary units are smaller than 100 nm (e.g. 1 micron agglomerates of 20 nm particles).

o They are virtually insoluble in water and do not disintegrate in the liquid of the organism or do so only very slowly.

o They are solid.

It should be stressed that if only part of the 3 criteria above is fulfilled materials can still be toxic but not specifically nanotoxic. For example, water soluble nanoparticles. In these cases, the conventional safety precautions should be acted upon.

Figure 1 shows the deposition number percentage of particles in specific regions of the human lungs.

Figure 1: Predicted fractional deposition (number%) of inhaled particles in specific regions of the human respiratory tract during nose breathing [Oberdörster et al., 2005].

Fig. 2 summarizes the criteria. A “formula” for nanotoxicity is given, which is to be interpreted only in a qualitative sense. It introduces nanotoxicity as a new category of toxicity, which may be superimposed on conventional toxicity. Note that conventional toxicity (Tox|conventional) basically implies dissolution, i.e. molecular dispersion of the toxin in the liquid of the organism, while nanotoxicity (Tox|nano cat and Tox|nano phys) is related to properties of the undisolved particle. Thus both categories can only coexist, if the solubility of the material is very small or if the particles are a mixture of soluble and insoluble components. The formula does not contain any synergy effects between the categories of toxicity and can be seen as an approach to the problem that must be further modified and refined as our knowledge increases. While Toxnano phys is considered as a purely physical property, an insoluble particle may also interact chemically through the phenomenon of heterogeneous catalysis represented into the term Toxnano cat.

Figure 2: Toxicity formula

3.2 Pyrophoricity

Due to their large surface-to-volume ratio and due to enhanced reactivity of a strongly curved solid surface, all oxidizable materials in the nanopowder state must be considered as potentially pyrophoric when in contact with air. Thus, explosive behaviour is possible. Little is known about nanoparticle pyrophoricity, so that we recommend to perform tests on small quantities of material before producing or handling quantities on the level of one gram or more. Laboratory studies have revealed that pyrophoricity, can, in some cases, be avoided, if the particles have already formed an oxide layer before exposure to atmospheric oxygen. It must therefore be certain that the tests are not performed on partially oxidized particles, while in the process an incident cannot be excluded, where a large, unoxidized sample is momentarily exposed to air.

4. Nanosafety recommendations

4.1 Handling of nanopowders

a) This should happen exclusively under a closed fume-hood or in an enclosed vessel (glove box). All parts that have been in contact with nanoparticles and spills should be cleaned afterwards (see below). If a closed fume hood is not available and the material is handled in an ‘open’ fume hood or other controlled ‘open’ environment, a FFP 3 or P3 certified mask should be worn.

b) Explosion safety: When handling quantities that exceed the milligram range, the pyrophoric properties of the nanopowder should be well known. For substances with unknown pyrophoric properties, these should be tested beforehand using mg quantities (see comments in paragraph 3.2).

c) Use good general laboratory safety practices as found in your chemical hygiene plan. Wear gloves, lab coats, safety glasses, face shields, closed-toed shoes as needed.