116104952
ARBOCATALOGUS NEDERLANDSE UNIVERSITEITEN
Onderwerp:
Good Practice #5
Gevaarlijke stoffen
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
V.C.L.Butselaar-Orthlieb@tudelft.nl
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.
Copyright:
Delft University of Technology, workgroup NanoSafety of the Faculty of
Applied Sciences.
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Contents
1. Introduction ...................................................................................................................................................... 3
2. Regulations and guidelines concerning nanoparticles presently available ..................................................... 3
3. Conclusions on nanosafety from the available literature ................................................................................. 5
3.1 Toxicity ...................................................................................................................................................... 5
3.2 Pyrophoricity .............................................................................................................................................. 6
4. Nanosafety recommendations ......................................................................................................................... 6
4.1 Handling of nanopowders.......................................................................................................................... 6
4.2 Handling of nanoparticle suspensions in liquids ....................................................................................... 6
4.3 Processing of nanoparticles in the gas phase: Gas Phase Nanoparticle Reactors .................................. 6
4.4 Continuous monitoring of the lab air ......................................................................................................... 7
4.5 Cleaning of vessels and nanoparticle contaminated objects .................................................................... 7
4.6 Disposal of Nanoparticles.......................................................................................................................... 7
4.7 Transport ................................................................................................................................................... 7
4.7 Summary ................................................................................................................................................... 8
5. Literature .......................................................................................................................................................... 9
5.1 General, Safety Issues in Nanotechnology ............................................................................................... 9
5.2 Nanotoxicology .......................................................................................................................................... 9
5.3 Particle Measurement ............................................................................................................................... 9
6. Acknowledgment ........................................................................................................................................... 10
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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
1
organizations as UNEP, UNIDO, UNESCO, ISO, IUPAC, CAS, OECD, ILO and the WHO.
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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.
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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 selfignite 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].
2
Nanoparticles may penetrate through commercially available gloves. Glove material is not the only criterion; elaboration
process and thickness are major issues as well. Advice: use at least 2 layers of gloves (see Nanosafe Report on
Effectiveness of Conventional Protective Devices).
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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 Tox nano 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.
Tox = Tox
conventional
Potential
Catalytical Toxicity
+ Tox
nano cat
+ Tox
nano phys
Small
Large
Soluble
Insoluble
Solid
Liquid
Potential
Physical Toxicity
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.
4.2 Handling of nanoparticle suspensions in liquids
Gloves that are suited for the liquid that is handled, should be worn to avoid contact with the skin. Take
care that dispersion of liquid droplets into the lab air is avoided.
4.3 Processing of nanoparticles in the gas phase: Gas Phase Nanoparticle Reactors
a) Use closed reaction vessels only, preferably at atmospheric or lower than atmospheric pressure. Make
sensitive leak checks between runs. When working under overpressure, obey the standard safety rules
for pressurized vessels and put the vessel into an enclosed safety vessel. For small over-pressure setups a closed fume hood is sufficient. If a closed fume hood is not available, obey the first point under
4.1.
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b) HEPA filters should be used on the exhaust side of the process before leading into the fume hood.
These filters should be tested periodically and replaced when their max. capacity is reached.
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.
4.4 Continuous monitoring of the lab air
A nanoparticle detector should be installed in every lab, in which gas phase work on nanoparticles is
carried out and where the quantity of nanoparticulate material exceeds a certain limit. We recommend a
limit of 1 μg/h. The monitor should give an alarm, if the concentration of particles smaller than 0.1 μm
rises significantly with respect to the laboratory background concentration, indicating a leak in a vessel.
The recommended detector is based on the principle of a charger-electrometer detector as proposed by
Schmidt-Ott et al. in 1999. An instrument of this kind is commercially available as a “Joint Length Monitor”
(TSI Inc., Minneapolis, Minessota, Figure 3). An alternative solution will be developed within the TU Delft.
This unit should contain a size separation mechanism so that particles < 0.1 m are essentially detected.
Figure 3: TSI AEROTRAK 9000 monitor (measures nanoparticle exposure)
4.5 Cleaning of vessels and nanoparticle contaminated objects
 All walls of reaction vessels that have been exposed to nanoparticles should be cleaned in the
following way:
o Vacuum cleaned, where the exhaust of the vacuum cleaner is equipped with a HEPA filter
and isn’t equipped with a pressure relive valve that bypasses this HEPA filter if blocked.
o Wiped with a wet cloth (use water or solvent); rinsing of the cloth with water. Always wear
gloves, to be disposed of.
o Always clean in a fume hood, and clean the fume hood after use.
o All contaminated material must be disposed of as chemical waste.
4.6 Disposal of Nanoparticles
 Quantities of nanoparticles (powders, colloids) exceeding the milligram range should be treated as
chemical waste, if the particle solubility in water is very small (inorganics like gold, TiO2, etc.)
 If the solubility is higher, the rules according to the toxicity class of the macroscopic material apply.
 Nanoparticle Residues in water from cleaning can be poured down the drain.
4.7 Transport
Transportation of nanoparticles can be done in the same manner as normal chemicals, i.e.: use closed
containers.
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4.8 Summary
The recommendations of this chapter are summarized in a Nanosafety ‘Quick Check’ (fig. 4).
Nano safety ‘Quick Check’
For research activities with “free nanostructured matter”
Index
3.1
Does the Nano material
have all the following
properties?

solid

primary unit < 100nm

insoluble in water
Thursday, September 11, 2008
No
You are handling
toxic nano material!
Yes
4.1
4.2
4.3
Processed in, or in contact
with any gas phase?
(e.g. Fluidization, solvent evaporation
using rotavap, bubbling through)
Treat as ‘normal’ Chemical
No
Treat as ‘normal’ Chemical
Yes
3.2
4.1
Pyrophoric properties known?
No
STOP, First test on the
smallest scale possible!
No
STOP, first arrange PPE
Yes
4.1
4.3
Use proper Personal Protective
Equipment (PPE)?
(goggles, lab-coat, gloves)
Yes
4.1
4.3
Material handled in a ‘closed’
fume hood or glovebox?
No
Material handled in an
‘open’ fume hood or other
controlled ‘open’
environment?
No
STOP, first arrange
proper workplace!
No
STOP, first arrange PPE
Yes
Yes
Do you use at least FFP3
or P3 certified mask?
Yes
4.3
Use closed reaction vessels
STOP, first arrange
closed vessel
No
Yes
4.3
Work at near atmospheric
pressures
No
Pressurized vessels into
an enclosed safety
vessel?
No
Yes
4.3
Is the exhaust gas filtered with
‘nano-HEPA’ filter?
STOP, first arrange
enclosed safety vessel
around your pressurized
vessel.
Yes
(e.g. Emflon PFR filter from Pall, > 3 nm)
Yes
4.3
Is the filter tested periodically?
No
Yes
4.4
Is the lab air monitored with a
cut-off size of 0.1 m?*)
4.5
4.6
Yes
No
Is the cleaning procedure arranged?
All exposed surfaces should be cleaned in the following way:

vacuum cleaned, where the exhaust of the vacuum cleaner
is equipped with a “nano-HEPA” filter**).

wiped with a wet cloth (use water or solvent)

clean in a fume hood and wear disposable gloves

cloth and gloves must be disposed as chemical waste

treat used solvent as (nano particle free) chemical waste
Yes
TNW
Nanosafety
Guidelines
Index
‘Almost’ Ready!
You are almost ready to handle the nano material. Use
your own knowledge and common sense to identify
further risks. Is the safety report authorised?
Workgroup Nano Safety
John Nijenhuis & Jelan Kuhn
STOP, first arrange
No
*) The monitor device
is under construction
**) The ‘nano vacuum’
cleaner is ordered and
will be validated before
use.
Both devices are
expected to be
available in 2009
(V.C.L.Butselaar-Orthlieb@tudelft.nl)
Figure 4: The summary of this guideline in a ‘Quick Check’
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5. Literature
5.1 General, Safety Issues in Nanotechnology
 A first UK Government research report, Department for Environment, Food and Rural Affairs,
Characterising the potential risks posed by engineered nanoparticles, Website: www.defra.gov.uk.
 WK8985 New STANDARD GUIDE FOR HANDLING UNBOUND ENGINEERED NANOPARTICLES
IN OCCUPATIONAL SETTINGS, ASTM International, by Subcommittee: E56.03, 08-23-2005. see
also the new (2008) active standard: ASTM E2535-07.
 COMMISSION OF THE EUROPEAN COMMUNITIES: COMMUNICATION FROM THE
COMMISSION, Towards a European strategy for nanotechnology, Brussels, 12.5.2004 COM (2004)
338 final
 Health Council of the Netherlands, Health Significance of Nanotechnologies (Gezondheidsraad),
2006 (English version: 2007).
 Gina Gerritzen, Li-Chin Huang, Keith Killpack, Maria Mircheva, Joseph Conti Advisors: Dr. Patricia
Holden, PI, Dr. Magali Delmas, Co-PI, Dr. Barbara Herr Harthorn, Co-PI, Dr. Rich Appelbaum, Co-PI,
A Review of Current Practices in the Nanotechnology Industry, PHASE TWO REPORT: SURVEY OF
CURRENT PRACTICES IN THE NANOTECHNOLOGY WORKPLACE, Produced for the International
Council on Nanotechnology By the University of California, Santa Barbara, November 13, 2006
 RJ Aitken, KS Creely, CL Tran, Nanoparticles: An occupational hygiene review, prepared by the
Institute of Occupational Medicine for the Health and Safety Executive 2004, RESEARCH REPORT
274.
 SCIENTIFIC COMMITTEE ON EMERGING AND NEWLY IDENTIFIED HEALTH RISKS(SCENIHR),
Opinion on The appropriateness of existing methodologies to assess the potential risks associated
with engineered and adventitious products of nanotechnologies, Adopted by the SCENIHR during the
7th plenary meeting of 28-29 September 2005, EUROPEAN COMMISSION, HEALTH & CONSUMER
PROTECTION DIRECTORATE-GENERAL, Directorate C - Public Health and Risk Assessment, C7 Risk assessment.
 Hood E: Nanotechnology: looking as we leap. Environ Health Perspect 2004, 112:A740-A749.
 ORGANISATION FOR ECONOMIC COOPERATION AND DEVELOPMENT, Report of the OECD
Workshop on the Safety of Manufactured Nanomaterials, Building Co-operation, Co-ordination and
Communication, Washington D.C., United States, 7th-9th December 2005, Environment Directorate,
Paris, 2006.
 EUROPEAN STRATEGY FOR NANOSAFETY, Nanosafe Report on Effectiveness of Conventional
Protective Devices: ‘Efficiency of fibrous filters and personal protective equipments against
nanoaerosols.’ Report available on: http://www.nanosafe.org/node/907.
 David Vervloet: Safety of nanoparticulate matter. Literature review report, Delft University of
Technology, 2005.
5.2 Nanotoxicology
 Paul J.A. Borm, Editorial: Nanomaterials: time for action, Tijdschrift voor toegepaste Arbowetenschap
(2005) nr 3.
 David Mark, NANOMATERIALS – a risk to health at work? First International Symposium on
Occupational Health Implications of Nanomaterials Palace Hotel, Buxton, Derbyshire, UK, 12 – 14
October 2004, Report of Presentations at Plenary and Workshop Sessions and Summary of
Conclusions.
 Günter Oberdörster, Andrew Maynard, Ken Donaldson, Vincent Castranova, Julie Fitzpatrick, Kevin
Ausman, Janet Carter, Barbara Karn, Wolfgang Kreyling, David Lai, Stephen Olin, Nancy MonteiroRiviere, David Warheit, Hong Yang , Principles for characterizing the potential human health effects
from exposure to nanomaterials: elements of a screening strategy This article is available from:
http://www.particleandfibretoxicology.com/content/2/1/8.
 Donaldson K, Stone V, Tran CL, Kreyling W, Borm PJ: Nanotoxicology. Occup Environ Med 2004,
61:727-728.
5.3 Particle Measurement
 Schwela, D. Morawska, L., Kotzias, D., (editors), GUIDELINES FOR CONCENTRATION AND
EXPOSURE-RESPONSE MEASUREMENT OF FINE AND ULTRA FINE PARTICULATE ATTER
FOR USE IN EPIDEMIOLOGICAL STUDIES, World Health Organization (http://www.who.int/peh/).
 Schmidt-Ott, Z.D. Ristovski, “Measurement of Airborne particles” in Indoor Environment, edited by
Lidia Morawska and Tunga Salthammer, Wiley-VCH, Weinheim, 2003, ISBN 3-527-30525-4, pp5681.
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
Schmidt-Ott A, Kauffeldt T 1999 Monitoring Particulate Air Pollution by Integrating Sensors. VDI
Bericht No. 1443, pp. 517, VDI Verlag, Düsseldorf, Germany.
6. Acknowledgments
The authors would like to thank Prof Paul J.A. Borm for his critical, scientific and pragmatic input.
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