Compendium of all conference presentations

Transcription

Twinning project "Chemical Safety 3" SI 06 IB EC 02
REPUBLIC OF SLOVENIA
MINISTRY OF HEALTH
CHEMICALS OFFICE
OF REPUBLIC OF
SLOVENIA
OPCW
CONFERENCE PRESENTATIONS
CONFERENCE ON NANO-SAFETY
April 22 – 24, 2009
Ljubljana, Slovenia
Twinning Project Chemical Safety 3, SI 06 IB EC 02
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Responsible Production and Utilization
of Nanomaterials in the Chemical Industry
– Applications, Voluntary Measures and Regulatory Context –
22 – 24 April 2009, Ljubljana
Dr. Hans-Jürgen Klockner
VCI (German Chemical Industry Association)
1. Applications of Nanomaterials
The value chain starts with the chemical industry
Materials
Anti-reflecting
treatment of glass
Components
Surface treatments
Products
Improvement of
fuel cells
(ceramic membranes)
Paint applications
OLED Techniques
CONFERENCE ON NANO-SAFETY, 22-24 April 2009, Ljubljana, Dr. Hans-Jürgen Klockner / VCI
3
Further nanotechnology/nanomaterial applications
Environmental Technology
Surface enhancement / Coatings
•
•
•
•
•
•
•
•
•
•
•
•
Solar cells
Thermal insulation of houses
Fuel cells
Hydrogen storage
LEDs, i.e. “cold light”
Flexible und low energy displays
Lower weight cars
Wind mill rotors…
(polymer-NM-composites)
Self cleaning surfaces
Scratch resistant surfaces
Technical textiles
Water purification
4
What are nanomaterials chemically?
Oxides
• of silicon, titanium, aluminum, zinc, iron, cerium…
Elements
• carbon allotropes (carbon black, carbon nanotubes, fullerenes), silver, iron…
Organic compounds
• vitamines…
Polymer-nanomaterial composites
These are all chemical substances: Just as fine powders or dispersions.
5
2. Voluntary Measures of the German Chemical Industry
Implementing Responsible Care® on Nanomaterials
Responsible Care ® is the chemical industry’s Code of Conduct
Responsible Care® applies to all products of the chemical industry
• i.e. also to nanomaterials
The Global Responsible Care® Principles require to:
• continuously improve HSE-knowledge and performance
of technologies, processes and products over their life cycles
• report openly on performance, achievements and shortcomings
• listen, engage and work with people to understand and address
their concerns and expectations
• cooperate with governments and organisations for effective
regulations and standards, and meet or go beyond them
• provide help and advice to foster the responsible management
of chemicals along product chain
7
General statements in laws vs. Codes of Conduct
REACH: “Manufacturers, importers, downstream users must ensure that
substances do not adversely affect human health or the environment.”
[German] Dangerous Substances Ordinance: “Manufacturers / importers
must classify substances / preparations according to their dangerous
properties (with obligation to take efforts to gather information).”
[German] Worker Protection Law: “Employer must take the necessary
measures for occupational health and safety (with obligation to verify
the efficiency of the measures and, if needed, to adapt the measures).”
[German] Product Safety Law: “No marketing of products if there are
risks for users at typical uses. Users must be provided with the
necessary HSE information.”
Language of laws is similar to that in Codes of Conduct.
Industry associations often write guidelines how to
implement laws.
8
8 VCI documents for a comprehensive but modular approach
Principles document
• Implementing Responsible Care® on Nanomaterials
Regulatory documents
• Nanomaterials and REACH
• Data Gathering for Risk Assessment
• Occupational Safety and Health
• Communication in the Supply Chain
• Standardization
Documents on Safety Research
• Human Health
• Environment
www.vci.de
This approach for responsible nanotech use is
reflecting the European legal environment and REACH
9
Voluntary measures in the VCI guidance documents
above legal requirements
For Risk Assessment quite a number of additional physicochemical
information on top of REACH requirements
In special cases (specific toxicity and/or widespread use and repeated
exposure) gathering of HSE information beyond REACH Annex VII
(i.e. from Annex VIII, IX und X)
Minimise exposure at the workplace, until specific limit values are laid
down for nanoparticles or certain nanomaterials
Safety Data Sheets for all substances/preparations
(i.a. also for those not classified as dangerous)
Intensifying safety research with specific projects
Stakeholder dialogues
10
VCI Stakeholder activities
The German chemical industry strives for an open dialogue with
society to address societal expectations and concerns
VCI Stakeholder Workshops on nanomaterials
(moderated by the Stiftung Risiko-Dialog, St. Gallen)
occupational safety aspects (2005 – 2007)
information flow in the supply chain (2008)
environmental aspects of nanomaterials (end of 2009)
Public Fora on nanomaterials in major cities
VCI is an active partner in the “Nano-Dialog” of the German
Environment Ministry
3. Regulatory Context
11
Occupational Safety and Health
D Nanospecific VCI / BAuA [German CA] guidance for the workplace
• Especially targeted to SMEs
• Explanation of legal requirements for workplace safety
• Checklist and recommendations:
Information of workers, technical safety measures,
personal safety equipment, substitution
Overview on exposure measurement techniques
Recommendation to minimise exposure at the workplace,
until specific limit values are laid down for nanoparticles
or certain nanomaterials
• And: The German chemical industry is very active
in SG 8 of the OECD WPMN (exposure measurement / mitigation)
13
CASG Nano to implement REACH on Nanomaterials
(DG ENT, DG ENV, CAs, ECHA, Industry, NGOs, Akademia…)
CASG Nano Advices
Deadline
0. Nanomaterials in REACH
Jan 2009
1. Carbon and graphite in Annex IV and V
Jan 2009
2. Substance Identification
Jan 2009
3. Registration of Nanomaterials (NM)
Spring 09
4. Advice on Classification and Labelling of NM
Spring 09
5. Communication in the supply chain
Dec 2010
6. Testing – Physico-chemical properties
7. Chemical Safety Assessment of NM
Dec 2010
8. Testing – Human health toxicity
9. ?Annex XIV - Authorisation of NM as SHVC
10. Testing – Ecotoxicity Environment
Dec 2010
11. Testing – Fate, Degradation, Aqueous Environment
12. Risk management measures
Dec 2010
13. Alternative testing methods for NM
14. Finalisation of REACH guidance
REACH rev.
15. Finalisation of testing strategies for NM
June 2012
16.CONFERENCE
Recommendations
for further
research
ON NANO-SAFETY,
22-24
April 2009, Ljubljana, Dr. Hans-Jürgen Klockner / VCI
14
Nanomaterials and REACH (1)
REACH
• regulates chemical substances, in whatever size, shape and form,
• therefore also regulates nanomaterials,
• and provides the necessary legal instruments for their regulation.
• REACH is underpinned by the Precautionary Principle (Art. 1)
D This is meanwhile common understanding
15
REACH Registration:
• Mandatory for all substances >1 t/a per registrant
• “Substances”, not uses or forms, must be registered
• All uses / forms of the substance must be identified in the registration
dossier
also uses / forms of the substance at nanoscale
even if they are < 1 t/a!
• Obligation for update, if a registered non-nanoscale substance
is to be manufactured also at nanoscale
D VCI guidance on the requirements of REACH for nanomaterials
16
Legal requirements within REACH without volume thresholds
and independent of registration timelines:
• Classification and labelling
DDifferent products with the same chemical identity can have
different classification / labelling
• Information in the supply chain according to Title IV of REACH
D Nanospecific VCI guidance for the Safety Data Sheet
17
Data Gathering for Risk Assessment
D Nanospecific VCI guidance for gathering of hazard information
• Aligned with OECD programme
• Tiered gathering of HSE information acc. to REACH Annexes VI – X
• Recommendation for additional physicochemical information
on top of REACH requirements:
surface chemistry/coating, morphology, crystalline phase, shape,
surface structure, specific surface area, particle size/size distribution,
agglomeration/aggregation in native material or in preparation, known
catalytic activity
in special cases: dustiness, porosity, dispersion stability in water (or in
other media), zeta potential (surface charge), photocatalytic activity,
radical formation potential
18
Communication in the Supply Chain
Legal requirement to submit information to downstream users
D Nanospecific VCI guidance for the information flow in the
supply chain by means of the Safety Data Sheet (SDS)
Common practice in the German chemical industry:
• Safety Data Sheets for all substances/preparations
i.e. also for those not classified as dangerous
19
Industry contributes to CASG Nano
Industry works closely with COM, ECHA and CAs
on a sound implementation of REACH on nanomaterials
Contents of industry guidance documents – like VCI‘s ones – may
find the way into ECHA guidance
20
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Orthopaedic implant
components as a source of
nanoparticles
Ingrid Milošev
Jožef Stefan Institute, Ljubljana, and
Valdoltra Orthopaedic Hospital, Ankaran,
Slovenia
Conference on NanoNano-Safety,
Safety,
Ljubljana, 2222-24 April 2009
Number of implants and devices for USA
(global numbers 2-3 times higher)
Type of implant
Number
Intraocular implants
Intraocular lenses
2.500.000
Contact lenses
30.000.000
Cardiovascular
implants
Pace makers
400.000
Vascular grafts
300.000
Stents
Heart valves
1.500.000
100.000
Orthopaedic implants
Total hip replacements
250.000
Total knee replacements
250.000
Dental implants
910.000
Biomaterial Science,
Science, B.D. Ratner,
Ratner, A.S. Hoffman,
Hoffman, F.J. Schoen,
Schoen, J.E. Lemons,
Lemons, 2004
IM1
Indications for total hip
replacement:
- osteoarthritis
- osteoarthritis secondary to
dysplasia
- aseptic femoral head necrosis
- rheumatoid arthritis
- post-traumatic arthritis
Radigraph image of THR:
(A) Post implantation
(B) Prior revision surgery – aseptic loosening with osteolytic
zones along the stem and changed cup position
Animation: http://www.wmt.com/
Survivorship curve is a
long-term indicator of
the successfulness of a
particular prosthesis.
Cum Survival
Cumulative survivorship
1,00
0,95
Data are created based
in the Valdoltra Register
of hip and knee
prostheses.
0,90
0,85
0,80
0,00
2,50
5,00
7,50
f
10,00
Time in situ / years
12,50
At 12 years postpost-op, 90% of
prostheses still implanted
826 hip revision operations in the period from 2002 to 2007
700
Number of revisions
600
585
500
71%
400
300
258
183
200
144
100
67
48
30
26
23
8
19
20
Pain
Fracture of
the
prosthesis
Other
0
Loosening Loosening Loosening Loosening
of acetab. of femoral
of both
part
part
parts
Deep
infection
Fracture of Dislocation Two-stage Osteolysis
the femur
revision of femoral
part
Reason for revision
Aseptic loosening related to the formation of wear debris and consequent osteolysis
is reason for revision in >70%.
Origin of wear
Surface wear damage
Wear particles
Polyethylene particles
Metal particles
Cement particles
Novel bearing combinations
Metal-on-metal
Ceramic-on-ceramic
Biological consideration of particulate
debris
Introduction
Wear debris
origin:
acetabular cup,
acetabular inlay
a
e
c
d
e
f
f
Mode 1: two primary bearing surfaces (a,b)
Mode 2: primary surface moving against a
secondary surface (c, d)
Mode 3: primary surfaces including third
particles
interposed (e, f)
b
Isolation procedure
by NaOH digestion
• For SEM analysis - filtrate the top layer through 0.2 um
polycarbonate filter paper and coat with gold
Metal particles
For SEM analysis – filtrate the bottom layer through 0.2
um polycarbonate filter paper and coat with gold
fibrilfibril-like
round (submicron)
submicron)
elongated fibrilfibril-like
Wear debris
%
75
70
65
60
55
50
45
40
35
30
25
20
15
10
5
0
0,1
0,5
1
5
More
Length of particles (micrometers)
Length of polyethylene particles isolated from implants with
different material of the femoral head
Wear debris
Metal particles
origin:
femoral head
femoral stem,
acetabular inlay
acetabular cup
www.endoplus
www.endoplus..com
SEM images of retrieved metal components
abrasion wear
change in geometry, fretting
30 um
third body wear
5 um
I. Milošev, R. Trebše, et al., JBJS.Am, 88 (2006)
1173-1182
Back-scattered SEM and EDS analysis of metal particles
Wear debris
Wear debris
Agglomerated and individual wear particles of
Ti6Al4V isolated from periprosthetic tissue
Bone cement particles (polymethylmethacrylate)
Wear debris
Cortical bone
Cancellous
bone
Bone cement
Polyethylene
Metal
ZrO2 or BaSO4 particles added to bone cement as
radioopaque agents.
agents.
Novel bearing
combinations
Size, composition and volume of wear
debris particles are dependent on the type
of bearing combination.
Wear of metal-on-metal bearings is lower
but particles are nanosized and their
number is up to 500 times the number of
polyethylene particles in conventional
bearings/per year !
1012 to x 1014 metal particles/
year
Wear debris
papain
digestion
Metal wear debris isolated from periprosthetic
tissue of metal-on-metal prosthesis by enzyme
digestion procedure
I. Milošev, M. Remškar, J. Biomed. Mater. Res, in
press
High-resolution
TEM
I. Milošev, M. Remškar, J. Biomed. Mater. Res., in
press
CoCr-O-particle
Biological response
Consequences of particles formation
Increase in total surface area
Local tissue response and release of
cytokines involved in bone resorption
Local tissue response
Biological response
B.F. Morrey,
Morrey, Biological,
Biological, Material, and Mechanical Considerations of Joint Replacement,
Replacement, 1993
Biological response
Systemic effects
Biological response
Systemic effect of metal particles– blood and urine
0,6
3
2,8
0,5
2
0,4
0,5
2,4
0,3
1
Serum Cr (ug/L)
Serum Co (ug/L)
0,2
0,1
0,4
0
200
400
600
0,3
2,0
0
0
200
400
600
1,6
1,2
0,8
0,2
control group
0,1
0,4
control group
0,0
0
100
200
300
400
500
600
700
800
900
0
100
200
days post-op
Hip prosthesis implanted
300
400
500
600
700
800
900
days post-op
2-year postpostop
I. Milošev, P. Campbell, V. Pišot, J.Orhop. Res., 23 (2005) 526-535
Biological response
Systemic effects
Transport of particles to distant organs
Potential for carcinogenesis and
hypersensitivity
Metal
sensitivity
Skin test for metal
sensitivity are not
correlative and are
unable to predict
delayed metal
hypersensitivity !
Willert HG et al., Osteologie (2000), World Tribology Forum in Artroplasty
(2001)
Delayed Type Hypersensitivity (DTH) related to the use of metal-on-metal
prostheses:
Diffuse and perivascularly oriented lymphocyte infiltration
Macrophages (sometimes with drop-like inclusions)
Plasma cells*
Infiltrates of B-lymphocytes*
Massive fibrin exudations*
Clinical status: pain
Concluding remarks

Benefits of total joint replacements are most
important fot the patient.

We should be aware, however, that loosened
implant components are a source of various
types of nanoparticles – metal, polyethylene,
PMMA and ceramic.

Knowledge on their morphology and
composition contributes to the understanding of
failure mechanism.

Efforts are directed to the prolongation of lifetime of implants by increasing their wear
resistance.

Joint collaboration studies between medical and
research community are necessary.
Acknowledgments
Orhopaedic surgeons at the Valdoltra
Orthopaedic Hospital (V. Pišot, R.
Trebše, S. Kova)
Vesna Levaši, MD, Arthroplasty
register
Prof. Andrej Coer, University of
Primorska, pathology specialist
Dr. Maja Remškar, Jožef Stefan
Institute
Thank you
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University of Modena and Reggio Emilia
Laboratory of Biomaterials
Italy
Clinical evidence of exposure to
environmental nanopollution
Antonietta M. Gatti
Antonietta.gatti@unimore.it
Nanosafety - Llubljana 2009
PM10
Nanoparticles
Red cells
Scale of dimensions of biological and synthetic materials
1
Nanosilver Technology
in washing machines, air conditioners, refrigerators
2
Nanotechnological T-Shirt
2Pm
MIPAN Nano Magic Silver is an anti-microbial that contains nanosized silver ions kill various harmful germs
The affair Magic-Nano
3
Chewing gum :
Happydent defensive
Chewing gum: Daygum Herbs White
4
Toothpaste
Nano-Up
Japan
Toothbrush
Nano-Up
Japan
5
Toothbrush Nano-Up
Japan
BRITA :
water filter device
6
BRITA
water filter
Sn Ca
Ag
BRITA
water filter system
7
Coordinator:
Dr. Antonietta M. Gatti
Consorzio Nazionale Interuniversitario
Sviluppo Materiali -CNISM
University of Modena & ReggioEmilia
Lab of Biomaterials, Dept.Neurosciences,
Via Campi 213 A- 41100 Modena- I
gatti@unimore.it
Development of an
Integrated Platform for Nanoparticle
Analysis to verify their possible
toxicity and the eco-toxicity
Partners
1.
University of Salzburg, A
2.
Fraunhofer Institute of Biomedical
Engineering, D
3.
Consiglio Nazionale delle Ricerche, I
4.
Università della Magna Graecia, I
5.
Grimm Aerosol, D
6.
VITO n.v. B
7.
CSEM SA, CH
8.
Institut Català de Nanotecnologia, S
9.
Joint Research Centre Ispra -EVCAM
University of Modena &
Reggio Emilia
8
is the branch of learning that
deals with how the organism
reacts to the presence of
micro- and nano-particles
•ESEM
FEG-ESEM
9
Lung
Nemmar et al.: Circulation 2002, 105:411
Passage of 100nm sized particles in the blood and in the liver
Pulmonary Mesothelioma
Asbestos fiber
10
228 BR
LUNG
Pulmonary
Mesothelioma
LUNG
Adenocarcinoma
11
129 AP
LUNG
Pluri-visceral Granulomatosis
SPLEEN
129 AP
Pluri-visceral Granulomatosis
LUNG
112K_011
12
RF 4
Nanoparticles of Gold in a liver granuloma.
The patient was treated with colloidal gold particles for
knee arthrosis.
10 Pm
112L_003
LIVER
13
Colon cancer
with clusters of Silver nanoparticles
Blood clot in vivo
Ag
14
Gulf-War
syndrome kidney
Hg
20 Pm
Cluster of nano Hg-Se
KIDNEY
112K_006
15
Barium-sulphate
nanoparticles found
inside a thrombus
10 Pm
10 Pm
BLOOD
Soldier’s wife
affected by Burning
Semen disease
Red cells
292
16
Glioblastoma
BRAIN
224A_006
Hodgkin’s Disease
SPERM
GW335C_002
17
Section of a lymph node
in a civilian of Sarajevo
affected by Hodgkin
Disease (FEG-ESEM)
5 Pm
Simulation of a “war” pollution exposure
18
Bladder Carcinoma in a mine-sweeper
BLADDER CANCER
W
19
Liver cancer
Fe
Si
ESEM image of sperm with a foreign body
spermatozoon
Lead nanoparticle
20 Pm
20
Impact of the environmental
nanopollution
Disease
21
Polveri sottili
Neu-Laxova syndrome
Neu-Laxova syndrome is a rare congenital
abnormality characterised by intrauterine
growth restriction, microcephaly, facial
dysmorphy, short neck, edema, scaly skin and
perinatal death. Additional features such as
spina bifida, cryptorchidism and shallow orbital
cavities have been reported.
Chromosomal analysis in reported cases has
revealed a normal karyotype and an autosomal
recessive inheritance has been postulated.
22
Liver
Kidney of a
malformed foetus
111 MA
Zn
Zn
_____20μ_____
23
Kidney of a
malformed foetus
Pb
Cl
Pb
____20μ______
AUT 77/06 - MANTOVA
Leucemia Mieloide Acuta
(n. int. 478 MN - 481 MN)
24
Kidney
Cuore
25
Debris found in the urban
pollution
5 micron
Foraminifero normale
foraminifero malformato
26
Malformed lamb from Sardinia
Kidney
MA
27
Liver
Brain
Gonads
Nano contamination in food
28
Bread
Tierra del Fuego
South America
Contamination in bread from Sicily
W Co Cd
W
W
29
Industrial Hamburger
Hay
30
Gas emission of a diesel car
CrFeNi
Ag
S. Domingo
Chocolate
31
From the fork to the farm
Bread from Modena
Cookie
Al Si Cl Os
W
W
32
Italian bread 1
Italian bread 2
Homogenized baby food
33
Peach skin
Clam
34
W
W
Cauliflower soup
35
Cauliflower soup
1000 Km
Anchovy’s liver from the Adriatic sea
Co Cr W Nb Nd
Cl Sb
36
Environment is polluted by airborne
nanoparticles, unintentionally released by high
temperature combustive processes.
Results of the research
37
FP5- European Project
NANOPATHOLOGY
Ni Group :
nodules observed on both
sides (particles + bulk
material) in all animals 6
months after implantation
Co Group :
Nodules observed on the left side
(nanoparticles IM) in all cases 8
months after implantation
– nothing on the right side (bulk
material implanted SC)
Co NPs
Nickel and Cobalt nanoparticles induced
rabdomiosarcoma after 6-month
implantation in rats,
the bulk samples only fibrotic capsules or
granulomas.
38
3T3 fibroblasts with Fe3O4 dry nanoparticles
“free” in the nuclear area of a mitotic cell
0.1 Pm
FP6- European Project-DIPNA
Factors influencing the pathogenicity of microand nanoparticles
PHYSICAL
Foreign body
Size
Shape
Surface area state
Concentration
Intake velocity
CHEMICAL
Composition
Corrodibility
Speciation
BIOLOGICAL
Organ (cell) involved
Health condition
Individual variability
Radioactivity
39
Thank you
Nanopathology: the health
impact of nanoparticles
Pan Stanford Publishing
www.worldscibooks.com/nanosci/v001.html
We cannot hide the problems
40
The ability to think differently today from yesterday
distinguishes the wise man from the stubborn.
J.Steinbeck (Nober Prize 1962)
41
22.-24. April 2009, Ljubljana, Slovenia
Nanosized ZnO and nano TiO2:
bioavailability and bioaccumulation
Damjana Drobne
University of Ljubljana, Biotechnical Faculty
Department of Biology, SLOVENIA
E-mail: Damjana.Drobne@bf.uni-lj.si
Research group for nanobiology and nanotoxicology
Dept. Biology, Biotechnical faculty, Uni Ljubljana
Damjana Drobne; Vladka Lešer; Janez Valant; Živa Tkalec Pipan;
Marjetka Kralj Kuni; Sara Novak, student; Tea Romih; student
______________________________________________
National Institute of chemstry
Anita Jemec
______________________________________________
Faculty for computer and information science, Uni Ljubljana
Jernej Zupanc
J1-9475 (C) Elaboration and evealution of a single species
toxicity test for nanoparticles with a terrestrial isopod
evaluation and Izdelava in vrednotenje testa strupenosti
(basic research project), Slovenian Research Agency
2006-2009
Aim of work
…. to study interactions between
nanoparticles and biological systes
In vivo and in vitro biological system
A terrestrial isopod, a model
invertebrate organism
Lipid vesicles
Our past experiences
... studding toxicity of metal pollutants and pesticides present
in the environment.
Present challanges
Interactions between nanoparticles and biological systems.
+
Photo: M. Bele, Institute of chemistry, Ljubljana
.. .biological potential of nanosized metal oxides
Chemicals affect target molecules or interfere with different intracellular
compartments. The effect is propagated upwards to higher levels of biological
complexity (cells, tissue, organs, organism) and it is manifested as toxic response.
What about nanoparticles?
1) One hypothesis is that nanoparticles
interact firstwith cell membrane!
A consequesnce is….
Photo: J. Valant
… cells are affected, but nanoparticles
were not detected inside the cells (nanoTiO2).
2) The other opened question is:
are nanoparticle bioavailable; do they bioaccumulate?
?
By L.Ziccardi, M. McArdle, Y. Lowney, J. Tsuji
Do ZnO nanoparticles accumulate?
Our work
- model organism, terrestrial isopod P. scaber
- food exposure to nanoparticles for 4 weeks
- comparison among bioaccumulation of
- nano ZnO,
- macropowder ZnO
- ZnCl2
Background
• terrestrial isopods accumulate high amounts of
meals (Zn, Pb, Cu, Fe etc). in their tissue
• a lot of knowledge already exist on the
accumulation pattern and accumulation strategy
of metals if offered as soluble salts
-
Experimental set up
+
Four weeks feeding on Nanoparticel,
macropowsder or
ZnCl dosed food
metal analyses in whole organism by AAS
concentrations of Zn in the body
Background knowledge: FIB/SEM,
Photo: F.Tatti, FEI
Scanning electron micrograph of macropowder of ZnO.
Scanning electron micrograph of nanosized ZnO
Results
no diffrences in amount of accumulated Zn
among groups
TOTAL BODY
1200
5000 μg/g
Amount of Zn (Pg/g dry weight)
•
1000
# glede Zn 2000 n
* glede na kontrolo
& glede Zn 2000 M
$ glede ZnCl 2000
$
&
2000 μg/g
800
#
*
*
*
600
400
200
0
control
Zn2000n zn2000M znCl2000 Zn5000n zn5000M ZnCl5000
Exposure concentration (Pg/g food)
By Ž. Pipan Tkavec, D. Drobne, A.Jemec ,T.Romih, P.Zidar, M.Bele
Discussion
• we are not able to answere the question about
nanoaprticle bioavailability or bioaccumauation
pottential
• the fact is that when nanosized or macrosized
ZnO is ingetsed an equal prtion of Zn is
accumulated as when ZnCl2 is inegested
Present/Future direction of research
• investigation of accumulation of other
nanparticles with lower dissolution rates; for
example Cu and Ag nanoparticles
• Investigation of interaction between membranes
and nanoparticles
Photo by J.Zupanc
Computer aided analysis of lipid vesicles shape transformations
after incubation with nanoparticles.
Publications:
-
DROBNE, Damjana, JEMEC, Anita, PIPAN, Živa. In vivo screening to determine
hazards of nanoparticles: nanosized TiO2. Environ. pollut. ,2009, issue 4, vol. 157,
str. 1157-1164
-
JEMEC, Anita, DROBNE, Damjana, REMŠKAR, Maja, SEPI, Kristina, TIŠLER,
Tatjana. Effects of ingested nano-sized titanium dioxide on terrestrial isopods
Porcellio scaber. Environ. toxicol. chem., 2008, vol. 27, no. 9, str. 1904-1914,
-
JEMEC, Anita, DROBNE, Damjana, TIŠLER, Tatjana, SEPI, Kristina. Biochemical
biomarkers in environmental studies-lessons learnt from enzymes catalase,
glutathione S-transferase and cholinesterase in two crustacean species. Environ. sci.
pollut. res. int., 2009, 11 str.,
Thank you for your
attention!
TP SusChem
Safety aspects of the nano TiO2
production and application
Presentation at the Nano Safety Conference
Ljubljana 22nd- 24th of April 2009
Antonín Mloch
Content
) Preface
) Risk assessment framework of nano TiO2
) Common activities of TDMA
) Ongoing iniciatives
) Relative risk assessment for the several
industrial fabrications of nano TiO2
) Conclusions
1
: World consumption of TiO2 : ~ 5 mil t/year
: World consumption of UF and nano TiO2 : 40 kt/ year
(including 25 kt /year DeNOx catalysts)
UF TiO2 has a long history of safe use in cosmetics products spanning
many decades (UV Attenuator )
Nano TiO2 are also used in catalysts,coatings for self-cleaning
windows,electronics,fotovoltaics and medicine
N Czech Republic – Precheza producer of the pigmentary TiO2
and development of production and application of the precursors for
catalysts , photocatalysts and UV absorbers
3 MARKETS REPRESENT 80% OF
MARKET SHARE
5%
3%
8%
Catalyst
10%
Electroceramic
Color Pigment
UV blockers
54%
Photocatalyst
Misellaneous
20%
40 000 Mt / Year estimated 2006
Spring 2008
2
The industry is responsible for the evaluation of
any such risks in production and application
Attention focuses upon the questions of risk assessment and
risk management within the first phase of application research
Definition and structure of nanomaterials, toxicological and
ecotoxicological behaviour of nanomaterials , exposure and
need for specific ”nanoregulation
NI Is the whole life cycle (workers – consumers – disposal to
the environment) under the control by the industry ?
N
Is there information enough and has the relevant information
distributed adequately?
Potential for exposure to nano TiO2
Risk = Hazard x Exposure
Adapted from Tsuji J.S. § all : Toxicological Sciences;2006 89,
No.1 ,42-50
3
Routes of exposure, distribution
and degradation of NSP
Adapted from Oberdörster G.: Inhalation Toxicology 2004
Adapted from Oberdörster G.: Inhalation Toxicology 16,2004,23-45
4
Common activities of TDMA
TDMA Ultrafine TiO2 Working Group : TDMA members + Ishihara,Tayca, Merck
N Assessment of substance risk is time consuming and
costly procedure,multidisciplinary approach.
N Developing of an extensive dossier of safety data and
other evidence which examine the various aspects of the
consumer safety of UF TiO2 EC Directive : TiO2 is safe
for use in cosmetic products at maximum concentration of
25 % in order to protect the skin
N Standartization of respirable dust measurement
N Review of Toxicology and Epidemiology of TiO2
literature
TDMA = Titanium Dioxide Manufacturers Association
A Sector Group of Cefic
Several basic studies sponsored by TDMA
Historical Cohort Study of Workers Employed in the
Titanium Dioxide Production Industry in Europe, Results of
Mortality Followup; Boffetta, et al; Department of Medical
Epidemiology; Karolinska Institute, Stockholm, Sweden,
January 2003
: Subchronic Inhalation Toxicity Study on Pigmentary Titanium
Dioxide in Mice,Rats ,and Golden Hamsters,
Chemical Industry Institute of Toxicology (CIIT),2002
:
: Subchronic Inhalation Toxicity Study of Ultrafine Titanium
Dioxide with Mice,Rats,and Golden Hamsters ,CIIT USA 2003
5
Inhalation Toxicology and
Epidemiology
Subchronic,
Subchronic, inhalation study CIIT
Centres for Health Research USA
Rats, mice and hamsters
Photocatalytic TiO2 (Degussa P 25),
25),
Aerosol concentrations of 0,5 , 2 or 10 mg/m3;6 hours/
hours/day,13
day,13 weeks
Main findings of inhalation study:
There is no evidence that titanium dioxide itself has toxic
properties,that would lead to cancer. This recent study leads us to
believe that titanium dioxide does not present a carcinogenic risk to
man at exposures experienced in the workplace.
The results of our two mortality studies are most powerful
evidence that UF TiO2 does not have a significant carnigonic
effect on the human lung.
The studies do not suggest an association between
occupational exposure to TiO2 and risk for cancer.
Studies on application of sunsreens containing UF TiO2 to
healthy skin revealed that TiO2 particles only penetrate into
the outermost layers of the stratum cornum,suggesting that
healthy skin is an effective barrier to TiO2
Oral,subcutaneous and intraperitoneal administration did
not produce a significant increase in frequency of any type of
tumor in mice and rats.
6
Occupational Exposure Limits
NIOSH,USA recommend new exposure limits
of 1.5 mg/m3 for fine and 0.1 mg/m3 ultrafine TiO2
as time weighted average concentrations for up to 10 hr/day during a
40-hours work week..
These levels will serve to minimize any risks that might be
associated with the development of pulmonary inflammation and
cancer.
TDMA opinion : the lower limit for the critical dose of UF TiO2 may
be as high as 2 mg/m3.Hence ,REL of 1,5 mg/m3 would be protective
for ultrafine exposures.
exposures.
Ongoing iniciatives
) In April, 2008 the European Commission requested additional
information for nanoscaled material in cosmetics especially for
TiO2 .The final dossier was submitted to EC 23.2.2009 .
) At the moment WG 4 of ISO Committee is preparing ISO/AWI
11937 Nanotechnologies - Nano-titanium dioxide as a technical
specification, consisting of two parts: characterization and
determination and material specifications of certain applications
(e.g. coatings, cosmetics, plastics, ceramics).
Under WPMN there have been selected 14 nanomaterials for
which data should be gathered. If no data exists, it should be
conducted by testing. Titanium dioxide is one of those substances
selected. TDMA participation and data gathering
WPMN= OECD Working Party on manufactured nanomaterials
7
UF TiO2 Manufacture and Processing
) The main difference between ultrafine and pigmentary titanium
dioxide is primary particle size.Primary particles form aggregates
and agglomerates.The primary particle is not normally present as
discrete particles
) The processes for manufacturing UF TiO2 are usually similar to
that of pigmentary titanium dioxide ,having adopted many of the
standard unit operations and process equipment from pigment
technology .
The UF and nano product can be sourced from the sulphate ,the
chloride,hydrothermal process ,flame pyrolization or sol-gel method
Process Flow Diagram of manufacture UF TiO2
Crystal
formation
Titanium Dioxide:
How it is made –
UV attenuation grade
zTypical
Precipitation
zProcesses
Titanium
Tetrachloride/
titanyl sulphate
Filtration
Purification
Milling
Coating
Milling
Thermal
Hydrolysis
Water
Cosmetic Oils
Dispersion
UV Attenuation
Dispersion
Grades
UV Attenuation
Powder
Grades
8
Relative risk assessment for the several industrial
fabrications of nano TiO2
) representative synthesis method was selected based on its potential for scale up
and near-term potential for large-scale production and commercialization .
) A list of input and output materials,and waste streams for each step of
fabrication was developed and entered into a database that included key process
characteristics such as temperarature and pressure.The physical/chemical
properties and quantities of the inventoried materials were used to assess
relative risk based on factors such as
volatibility,carcinogenity,flammability,toxicity,and persistence
The protocol ranks three categories of risk relative to a 100 point scale
(where 100 represents maximum risk) :
incident risk,normal operation risk and latent contamination risk
Product ,manufacturing method
Risk score for
production
process
Nano TiO2 through hydrolysis and
calcination from TiCl4
Nano TiO2 by hydrothermal process
62
Nano TiO2 through hydrolysis and
calcination from titanylsulfat
Refinered petroleum
56
aspirin
58
64
76
9
Conclusions from risk assessment
) The manufacture of nano TiO2 may present lower risks than of
those of current activities such as petroleum refining, polyolefin
production, and synthetic pharmaceutical production
) Almost as much as constituent substances in a process, differences
in handling operations could have a marked effect on the final risk
N
scores
Recycling and successful recapture of materials play a key role in
lowering normal operations risk score.
Risk Assessment of exposure to TiO2 nanoparticles
location
hazard
exposure
risk
black session
Minimal of the TiO2
is present as free
particles
zero
zero
up calcination
as above
zero
zero
calcination
The presence of
nanoparticles is higly
unlikely
micronisation
minimal because all
the UF particles are in
aqueous suspension
final powder
product
The hazard is
potentially there but
indications are that
the dust is essentially
aggregated
Minimum exposure minimalize
during normal duties
zero exposure
Exposure levels need
to be established by
the manufacturers
zero
possible
10
Results for safe procedures for handling nano TiO2
The main hazards of the production and application of nano
TiO2 are physiological hazards, i.e. by inhalation
Potential dust exposure occurs only in specific areas of the
plant
Safe procedure for manufactiring and handling nano TiO2
have defined for each phases of activity
Wastes of nano TiO2 are not considered hazardous for
disposal into sanitary landfill or industrial waste disposal
landfill.
Conclusions
The safety of nano TiO2 has been the subject of numerous
experimental and clinical studies and has been fully demostrated.
These studies show no adverse systemic effects with nanoscale
titanium dioxide; no skin penetration detected, no skin irritant or
sensitising potential, no genotoxic potential, no toxic potential by the
oral route, no ecotoxicological potential.
Low potential to produce tissue inflammation by inhalation.
Limited human data are limited, quantitative data are available from
rodent studies.To use these data in risk assessment ,a reasonable
approach for extrapolating the rodent data to humans is required.
Use the best information available to make interim
recommendations on occupational safety and health practises in the
production and use of nano TiO2
11
These interim recommendations will be updated as appropriate to
reflect new information
They will address key components of occupational safety and
health, including monitoring, engineering controls, personal protective
equipment, occupational exposure limits, and administrative controls .
Additional are required to make a better assessment (for example
NIOSH plans to study airborne exposures to fine and ultra-fine TiO2
along with workplace procedures and end useres in comparison with
unexposed workers ;last year European Commission requested of
additional information for nano TiO2 in cosmetics.)
TDMA members take all possible precautions against all potential
work place exposures and support the continuous improvement of
procedures and processes to minimalize any potential exposure
NIOSH= National Institute for Occupational Safety and Health,USA
Thank you for your
attention
antonin.mlcoch@precheza.cz
Author acknowledge partial support for this work from Ministry of Industry
of the Czech republic within the framework of state programme TANDEM
12
Detection of nanoparticles
Maja Remškar1, Ivan Iskra1, Janja Vaupoti1, Griša Monik2
1Jozef
Stefan Institute, Jamova 39, Ljubljana, Slovenia
d.o.o., Kamniska 41, Ljubljana, Slovenia
2Aerosol
1.
Special properties of nanoparticles
2.
Direct observation of nanoparticles
(microscopy)
3.
Indirect observation (scattering)
4.
Detection of nanoparticles
5.
Demonstration of nanoparticle detectors (Ivan
Iskra, Grisa Mocnik)
Number of NPs in cm3:
Eye: resolution - 0.1 mm
-Office: 1.104- 4.104
Optical microscope: 300 nm (3000 x)
-Welding (varjenje) : 4.106
Unvisible
-Grinding (brušenje): 2.105
Transmission electron microscope:
0.12 nm – 1.5.106 x
-Smoking >1.108
exahalation
Airborn
Fast
NANOPARTICLE
Brownian motion
velocity v m-1/2 v r – 3/2
Reactive
mCarbon (10 nm) = 3.10-22 kg
v (RT) = 11 m/s
- Large surface area/mass ratio
- Quantum effects
Agglomeration of nanoparticles
- Self-assembly
of MoxSyIz
nanotubes
- Agglomeration of
TiO2 during the
production process
50 Pm
Agglomeration of WOx nanowires
during evaporation of solvent
2 nm
NO data on agglomeration
and recrystallization in:
• bio-compatible solvents
• during the transition
through the cell membrane
• inside the cell and its
nucleus
Chemical activity of nanoparticles
Strongly depends on the ration of surface atoms to volume atoms
Diameter
NS / NV atoms
8 nm
7%
1 nm
58 %
Physical and Chemical properties of
nanoparticles could influence their potential risk.
• Composition
• Size
• Shape
• Surface properties (possibility of adsorbed
spieces)
• Bulk properties- chemistry
Origin of nanoparticles and where we meet them:
• intentionally produced - engineered: cosmetics, food, detergents, textile, water
protective films
• non intentionally produced:
- a side product in industrial production (grinding, soldering, milling)
- combustion of bio-mass
- emission from diesel engines
• natural: erosion, desert powder, viruses
FROM EVER
Nanoparticles have always been present
in the environment
Combustion processes in the last 200
years have added to the amount of
manmade nanoparticles entering the
environment
• How can we determine and measure this?
• Is the overall amount of nanoparticles in the environment set to increase?
Workplace exposure
Large concentrations of nanoparticles may be present in occupational environments,
which deserve particular attention from the standpoint of exposure.
Limited data and guidelines are available for handling nanoparticles in occupational
settings as well as research laboratories.
For example, guidelines for the selection of respiratory protection for specific types of
nanoparticles are lacking.
A number of organisations including CEN, ISO or
OECD are working to develop and standardize
instruments and test methods for the support of
appropriate health, safety and environment legislation
and regulations of nanomaterials. It includes work on the
development and standardisation of:
· Instruments and test methods for measurement and
identification of airborne nanoparticle in the workplace
and the environment;
· Test methods to characterize nanomaterials;
Powered blouse respirator · Protocols for toxicity and eco toxicity testing;
www.nanosafe.org
· Protocols for whole life cycle assessment of
nanomaterials, devices and products;
· Risk assessment tools relevant to the field of
nanotechnologies;
· Test methods to assess the performance efficiency of
engineered and personal control measures;
· Occupational health protocols relevant to
nanotechnologies.
STM-Scanning tunneling microscope
-for studying surfaces at atomic level.
-for good resolution is considered to be 0.1 nm lateral resolution and 0.01 nm depth
resolution
www.iap.tuwien.ac.at
www.ijs.si
10
Atomic Force Microscopy
Carbon nanotubesnon-contact AFM
http://mrsec.wisc.edu
15 nm TiO2
Sigma-Aldrich
Interdepartmental Center for
Electron Microscopy,
IJS:
JEM-2010F, 200 keV
Light scattering
Large particles: small angle of
scattering
Small particles: large angle of
scattering
Dynamic light scattering
By knowing the incident
light frequency and
measuring the scattered
light frequency to
determine the shift, we
can calculate particle
size
Detection principles
Detection
Condensation
Electrometers
Number
concentration
Number of
particles
Net charge
Corona
discharge
Tailpipe
Current carried away
by particles
Exhaust flow
Electrometer
15-500 nm
Max 105 NPs/cm3
Prize: 7.000 Eur
High
voltage
source
Virtual
ground
Dekati ETaPS sensor for diesel exhaust
Current Monitoring Method
Condensation Particle Counter (CPC)
• Old technology--based on cloud chamber effect
• Grow nm particles in saturated alcohol or water atmosphere
• Then use optical counter to determine number concentration
• First widespread application was in clean rooms
• Needed to count very low levels
• CPCs are now common in air pollution research studies and to monitor
industrial processes
• CPCs in routine air monitoring are novel-currently no widespread use
in routine monitoring
• Results are model specific!
• No explicit upper size cut
• Performance in smallest sizes is model specific
Size distribution
Impactors
Air inlet
Cascade impactors are designed for a particle
size related sampling of ambient and industrial
aerosols. Weight or mass size distributions of
nanoparticles are obtained.
www.dekati.com
www.ki.si
16
Size distribution of
nanoparticles
TSI model
Particle Size Range:
10 to 487nm
Concentrations: up to
1.107 NPs / cm3
Price: cca. 50.000 Eur
Differential mobility analyzer
Condensation particle chamber
Electrostatic Low Pressure Impactor
6 nm – 10.000 nm
Max: 10 8 NPs / cm3
Prize: 75.000 Eur
GRIMM SMPS (dr. Janja Vaupoti, JSI)
Measurements of aerosol concentration and their size distribution in the range 10 – 1100
nm were carried out at different locations. Scanning mobility particle sizer (SMPS+C;
GRIMM Aerosol Technik) was used. The system consisted of the condensation particle
counter (CPC) and electrostatic classifier (L-DMA), without the neutraliser.
Laboratory 1
cleaning
open window
Laboratory 2/Office – next to workroom
open window
Workshop (metallurgy)
end of working hours
start of working hours
Parking place
end of
working day
evening
morning
Monitoring results in IonBond, UK
Background sample before vacuum
system opened
Vacuum chamber door opened –
first 6 minutes
after 9 minutes
after 30 minutes
Monitoring at workplace
1. Personal sampling: Exposure integration or alarm for personal use. Daily to
monthy analysis.
2. Mobile device: New operations, maintenance. Response time: 5 min.
3. Work places: Monitoring tool for data collection and alarm. Response time: 530 min.
4. Efficiency of collective protective equipments. Qualification after new filter
installation.
5-6: Drain: Environmental protection in the liquid drain.
7-8: Extraction: Environmental protection in the air.
9: External: 2 different needs:
• Monthly survey of the impact of the factory on the environment (routine and
accidental situations)
• Real time determination of the fluctuation of the external background noise in
order to correct inside measurements
Conference on nano-safety
17:00, 23.04.09
Guidance on handling and use of nanomaterials
23.04.2009
Miriam Baron
Federal Institute for Occupational Safety and Health, Germany
Overview
• Questionaire
• Guidance for Handling and Use of Nanomaterials at
the Workplace
• Threshold limit values
23.04.2009
• Nanodialog
Miriam Baron, Gr. 4.6, BAuA, Germany
1
17:00, 23.04.09
BAuA-questionaire 2006
• Initiated by the stakeholder dialog event on
engineered nanoparticles (october 2005)
• Cooperation with:
• German Chemical Industry Association (VCI)
• Federation of German Industries (BDI)
• 217 companies participated:
• Industry
23.04.2009
• Small and medium enterprises
3
• Research companies
4.6/Baron
BAuA-questionaire 2006:
Situation in Germany
• Participation according to the criterion: use of
nanomaterials above 10 kg/yr
• 45 companies participated:
• 51 % use above 100 kg/yr
• Thereof 11 % above 100 t/yr
• Thereof 7 % above 1000 t/yr (e.g. carbon black, silicic
acid)
23.04.2009
• 56 % produce/use more than one nanomaterial
4
• 71 % less than 10 exposed employees
• Reported products: 70
4.6/Baron
2
17:00, 23.04.09
Questionary: Activities (out of 70 products)
96 working situations:
• 37 mixing and dispersing
• 31 filling and baging
• 17 loading and decanting
• 7 drying
23.04.2009
• 4 milling
Multiple responses possible
5
4.6/Baron
Questionary: Knowledge gaps (out of 70
products)
• No knowledge on particle size and number
59
• No measurement (unknown exposure)
31
• No knowledge about potential health effects
28
23.04.2009
No particle-specific health complaints among the
workers were reported
6
4.6/Baron
3
17:00, 23.04.09
Questionary: Protection measures (out of 70
products)
Protection Measures
54
• Ventilation
63
• Personal protective equipment
(respiratory protection)
55
23.04.2009
• Engineering controls
7
4.6/Baron
Questionary: Protection measures –
Engineering Controls
23.04.2009
Engineering controls (54 cases)
8
• Wet processing
37
• Closed system
27
• Automatic processing
13
4.6/Baron
4
17:00, 23.04.09
Questionary: Protection measures ventilation
23.04.2009
Ventilation (63 cases)
9
• Open ventilation
29
• Semi-open ventilation
21
• Automatic ventilation
18
• Closed ventilation
13
• Natural ventilation
9
4.6/Baron
Questionary: Protection measures –
personal protective equipment
• For 80 % of the activities: usage of respiratory
protection (additionally to engineering controls and
ventilation)
• Wide spectrum, ranging from general masks to
23.04.2009
specific respirators (FFP1 to FFP3)
10
4.6/Baron
5
17:00, 23.04.09
Guidance for Handling and Use of
Nanomaterials at the Workplace
• Cooperation with the German Chemical Industry
Association (VCI)
• Published 2007
• To be updated this year
23.04.2009
• To be amended by industry sector specific
Guidance (under progress: for laboratories)
11
4.6/Baron
Contents
1 Introduction
2 General occupational health and safety rules
3 Recommendations for workers' protection in the
handling and use of nanomaterials
4 Current situation and development of measuring
methods for nanoparticles
23.04.2009
Annex
12
Flowchart on Hazard Assessment for
Nanomaterials at the Workplace
4.6/Baron
6
17:00, 23.04.09
General occupational health and safety rules
Duties according to the Hazardous Substances
Ordinance:
Information gathering
2.
Hazard assessment
3.
Determination of protection measures
4.
Review of effectiveness of measures
5.
Documentation
23.04.2009
1.
13
4.6/Baron
• Used product
(properties, volume, type and form of use).
23.04.2009
• Activity
(possible intake: by inhalation, dermal or oral).
For oxidizable materials, also fire and explosion
risks must be included
14
• Substitution options (including any use of processes
or preparations of the substance that result in lower
hazard)
4.6/Baron
7
17:00, 23.04.09
• Effectiveness of protection measures already in
place
• Implemented activities in preventive occupational
medicine
23.04.2009
• In case of data gaps, this lack of information must
be adequately taken into account when determining
protection measures.
15
4.6/Baron
STOP-Principle
1. Substitution options
2. Technical measures
3. Organizational measures
23.04.2009
4. Personal protection measures
16
4.6/Baron
8
17:00, 23.04.09
• Review of measure effectiveness in place
• Comparative inspection with measurement
• Documentation
• Firstly hazard assessment including:
• Substances used
• Working conditions
• Protection measures taken
23.04.2009
• Available measurement data
17
• To be used for assessment at a later stage
4.6/Baron
Substitution options
• Replacing health-endangering substances or
technical processes by less ones
• Binding powder nanomaterials in liquid or solid
media
23.04.2009
• Using dispersions, pastes or compounds instead of
powder substances wherever technically feasible
and economically acceptable
18
4.6/Baron
9
17:00, 23.04.09
Technical protection measures
Contained installations, wherever possible
• Otherwise avoid the formation of dusts or aerosols
• Extract possibly forming dusts or aerosols directly at
their source (e.g. in filling and emptying processes)
23.04.2009
• Ensure regular maintenance and function testing of
extraction facilities
19
• No recirculation without exhaust air purification
4.6/Baron
Organizational protection measures I
• Instructions to the workers, including
• Specific physical properties of free nanoparticles
• Need for special measures
• Potential long-term effects of dusts
• Relevant information in the operating instructions
• Limitation of exposed persons
23.04.2009
• Keep the number of potentially exposed workers as small as
possible (e.g. by time arrangements)
20
• Deny unauthorized persons access to the relevant work areas
4.6/Baron
10
17:00, 23.04.09
Organizational protection measures II
• Ensure clean work wear
• Work wear must be cleaned by the employer
• Work wear and private clothing must be stored separately
• Ensure the regular cleaning of workplaces
• Removing of deposits or spilled substances by
• Suction device
23.04.2009
• Wiping up with a moist cloth
21
• No blowing for removal
4.6/Baron
Personal protection measures
• Only where technical protection measures are not
sufficient or cannot be put into place
• Depending on substance properties
• Protective gloves
• Protection goggles with side protection
• Protective clothing
23.04.2009
• Respiratory protection equipment
22
4.6/Baron
11
17:00, 23.04.09
Personal protection measures (respiratory
protection)
• Efficacy of filters increases with decreasing particle
size in the size range between 2-200 nm
• Measuring data from BGIA
(on sodium chloride particles from 14 to 100 nm)
23.04.2009
• “Total number penetration efficiency"
P3 filters penetration less than 0.026% (particle count)
P2 filters penetration of 0.2% (particle count)
23
• Effectiveness must be reviewed
4.6/Baron
Personal protection measures (dermal
protection)
• Selection of gloves:
• Material must be suitable
• Material must fulfill requirements for maximum wearing time
under practical conditions
• Permeation time is important relevant criterion
23.04.2009
• Additional protection of other areas of skin by
24
• Protective suits
• Aprons
• Boots
4.6/Baron
12
17:00, 23.04.09
Further protection measures
• Depending on the properties of specific nanomaterials
• Anti-explosion measures in the handling of oxidizable
nanomaterials
• Specific protection measures in the handling of
reactive or catalytic nanomaterials
23.04.2009
• Conventional measures resulting from the hazard
assessment
25
4.6/Baron
Flowchart: Hazard assessment for Nanoparticles at the
Workplace (respiratory route)
Specific hazard
assessment
No
Yes
Risks due to explosions,
reactive or catalytically
active nanoparticles?
Work in extractor,
requirements
according to TRGS 526
General occupational
Hygiene measures
No Hazard
Yes
Does the activity involve
dust formation?
No
Yes
Activities in laboratories
or small volumes?
Is there a low hazard?
Yes
No
No
Open systems?
No
23.04.2009
Yes
26
Organizational measures
Personal protective
equipment
Sucking up
with integrated or
highly efficient equipment?
Yes
Efficiency testing in regular
intervals, instruction,
demarcation of work area
Process avoids dust
and aerosol formation
because of closed system?
No
Yes
Efficiency testing in regular
intervals, instruction
No
Can dispersion,
solid granules,
compounds be used?
Yes
Examine substitutions
options
4.6/Baron
13
17:00, 23.04.09
Hazard assessment
With respect to:
• Substance related hazards including
• Properties
• Physical state
• Processing options
23.04.2009
• Further hazards (e.g. electrical or mechanical)
27
4.6/Baron
Hazardous Substances Ordinance - Principles
Risk assessment by the employer before starting activities
•
Eliminating Risks
•
Minimize Risks
In case of uncertainty:
23.04.2009
•
28
Precautionary principle
„The need for control measures increases with both the
level of possible harm and the degree of uncertainty.“
4.6/Baron
14
17:00, 23.04.09
European Community/German Legislation
Placing on the market:
REACH (European regulation 2006/1907/EC)
• Applicable for nanomaterials
• With reference to the substance
• (optionally) consideration of the nanoform in the Chemical Safety
Report (CSR)
• if necessary additional proofs concerning the special nanoform
23.04.2009
Handling:
29
Hazardous Substances Ordinance
(based on European directive 98/24/EC)
4.6/Baron
Data gaps (TRGS 400/TRGS 526)
Minimal hazard properties in case of uncertainties:
R20/21/22
R38
R43
R68
Harmful by inhalation,
in contact with skin and if swallowed.
Irritating to skin
May cause sensitization by skin contact
Possible risk of irreversible effects
23.04.2009
Unknown new substances in research:
Toxic by inhalation, in contact with skin and if swallowed
30
Additionally: corrosive, (spontaneous) flammable,
explosive
4.6/Baron
15
17:00, 23.04.09
Information down the supply chain
Technical Data Sheet for Application
Material Safety Data Sheet
23.04.2009
Accompanying Letter
31
4.6/Baron
Material safety data sheet (MSDS)
• Information about substance properties and
occupational safety measures.
• Problem:
Handling of nano properties is not regulated
• Usual MSDS states:
“This substance has no dangerous properties”
23.04.2009
• Standard test methods are used to derive risks
32
• Measures are not justified with risks
4.6/Baron
16
17:00, 23.04.09
Existing threshold limit values (TLV’s)
TLVs for poorly soluble dusts/fibers with specific toxicity
•Quartz:
•Silver (metal):
•Asbestos:
0.075
0.01
0.01
– 0.3
– 0.1
–2
mg/m³
mg/m³
fibres/cm³
Generic TLVs: dusts with no specific toxicity
• Inhalable dust/total dust
:4
- 15 mg/m³
• Respirable fraction (fine dust, lung) : 1.5 - 10 mg/m3
23.04.2009
e. g. for titanium dioxide, graphite, iron oxide
Covering also the nano sized fraction
•
Legally binding TLVs specifically for nanomaterials are very rare
(Amorphous silica: 2 to 6 mg/m³)
33
4.6/Baron
Approaches for setting a TLV for
nanomaterials (1)
Draft exposure limits from NIOSH (USA, 2005)
for titanium dioxide:
23.04.2009
•
•
•
34
•
•
Nanoscale titanium dioxide: 0.1 mg/m3
Microscale titanium dioxide: 1.5 mg/m3
Potency factor 15 between nanoparticles and
microparticles based on long-term in vivo studies
Reduction of risk of lung cancer below 1 in 1000
Surface determines toxicity potential
4.6/Baron
17
17:00, 23.04.09
Approaches for setting a TLV for
nanomaterials (2)
Benchmark levels (BL) from BSI (UK, 2007) for four
classes of nanomaterials
Nano-BL
•
Fibrous nanomaterials (high aspect ratio): 0.01 fibres/cm3
Nano-BL in relation to established TLVs
Insoluble nanomaterials:
CMAR nanomaterials:
Soluble nanomaterials:
0.066 of TLV (NIOSH relation of 15)
0.1 of TLV
0.5 of TLV
23.04.2009
•
•
•
35
4.6/Baron
Nano dialog
• Stakeholder dialog:
NGO, Researcher, Industry, Other involved persons
• Leaded by the Nano commission
(temporary project group)
• Three Working parties on
• Chances for environment and health
• Risks and safety research
• Principles for a responsible use of nanomaterials
23.04.2009
• First period 2006 – 2008, will be elongated to 2010
36
• First Report just released
4.6/Baron
18
17:00, 23.04.09
Nano commission: Five basic Principles
for a Responsible Use of Nanomaterials
1. Defined Responsibility and management disclosed
(Good Governance)
2. Transparency regarding nanotechnology relevant
Information, Data and Processes
3. Willingness to the dialogue with Interest groups
23.04.2009
4. Established Risk management
37
5. Responsibility down the supply chain
4.6/Baron
Thanks to
My co-workers at BAuA
• Dr Torsten Wolf (Hazardous substances management)
• Dr Rolf Packroff (Hazardous and biological substances)
• Dr Bruno Orthen (Toxicology)
• Judith kleine Balderhaar (Database research)
• Sabine Plitzko (Measurement)
23.04.2009
• Dr. Eva Lechtenberg-Auffahrt (Occupational safety)
38
4.6/Baron
19
17:00, 23.04.09
Further questions:
Miriam Baron
Federal Institute for Occupational Safety and Health (BAuA)
Unit 4.6 “Hazardous Substances Management”
Friedrich-Henkel-Weg 1-25
D-44149 Dortmund
Germany
23.04.2009
mail-to: baron.miriam@baua.bund.de
39
www:
http://www.baua.de
4.6/Baron
Useful links/sources
Questionaire:
http://www.baua.de/nn_49456/en/Topics-from-A-to-Z/Hazardous-Substances/Nanotechnology/pdf/survey.pdf
Guidance:
http://www.vci.de/Default2~cmd~get_dwnld~docnr~121306~file~LeitfadenNano%5Fengl%5FFINAL%2Epdf.htm
Nano-Dialog:
http://www.bundesumweltministerium.de/english/nanotechnology/nanodialog/doc/40549.php
Other:
http://www.baua.de/en/Topics-from-A-to-Z/HazardousSubstances/Nanotechnology/Nanotechnology.html?__nnn=true&__nnn=true
http://www.ilo.org/public/english/protection/safework/ctrl_banding/toolkit/other_toolkits/nanotool_synopsis.pdf
http://www.bmu.de/gesundheit_und_umwelt/nanotechnologie/doc/37643.php
http://www.baua.de/nn_39406/en/Topics-from-A-to-Z/Hazardous-Substances/TRGS/pdf/Hazardous-SubstancesOrdinance.pdf
23.04.2009
http://www.vci.de/template_downloads/tmp_VCIInternet/122301Guidance%20SDS%20for%20Nanomaterials%20
_06%20March%202008~DokNr~122301~p~101.pdf
40
http://www.bmbf.de/en/nanotechnologie.php
4.6/Baron
20
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Nano-Safety:
Some Future Perspectives
Conference on NanoNano-Safety
2222-24 April, Slovenia, Ljubljana
Bjorn G. Hansen
dHoU Chemicals, DG ENV, European Commission
Chair, OECD Working Party on Manufactured Nanomaterials
Contents
1.
2.
3.
4.
5.
Introduction
Problems are not new – the solutions are
OECD WPMN – what’s next
EU Legislation – what’s next
Conclusions
1
1. Introduction

If given the choice, everyone would chose to
live in a pristine environment
Our standard of living is dependent on our
human activities, but all human activity results in
some level of pollution
So environment and health policy is all about
finding the balance between these two factors
2. Problems are not new – the
solutions are

Environment and Health policies are (generally) based
on science, but science and policy do not (generally)
develop in perfect co-ordination

2 example from the “chemicals area” where policy
needs outran scientific knowledge: endocrine
disruptors and REACH

Many more: C&L (Dir 67/548), RA (Reg 793/93)
2
solutions are

The case of endocrine disruptors: Policy concern
for the long term effects of exposures to
endocrine disruptors triggered significant
research activities and a re-assessment of current
chemicals policies
Results:

Validated OECD Test Methods
Re-assurance that (generally) current regulatory
systems can identify endocrine disruptors
Further research
solutions are

So, up to recently, policy drove (regulatory)
scientific research and awaited the outcome.
However,

Commission given 4 years to develop legislative
criteria for identifying PPPs as EDs
and so the pressure is on (again)!
3
solutions are

The case of REACH: Policy concern (among
others) for un-tested substances triggered a
system for generating sufficient information to
assess all chemicals manufactured or imported
into the EU
Results: Legislative

Legislative frame developed, but science needs to fill
(part of) this frame, e.g., category approaches
(including QSAR), exposure scenrios, DNELs, …..
solutions are

So (chemicals) policy drives (regulatory) scientific
research to enable implementation.
However,

To utilise fully the potential of “alternative”
information, much more research is needed
For many substances (petroleum substances, metals,
waste streams, ….), details need to be sorted out
(what should be tested, how to test, how to measure,
what to measure, …….)
and so the pressure is (still) on!
4
solutions are
Lessons learned:
Problems are not new
The solutions are new
The way to get solutions is not new
Questions are:
If and when policy will require action (regulatory
or voluntary)
How far have we reached in finding scientific
solutions
3. OECD WPMN – what’s next

Thanks to Jim Willis (U.S. E.P.A. and first
WPMN Chair) and the OECD Secretariat
Nanosafety Team for getting us as far as we
are today!!!!

OECD WPMN is about co-operating on the
(regulatory) science, developing common
(regulatory) scientific understanding, using
the well established “learning by doing”
approach
5
SG 5: Co-operation on Voluntary Schemes and Regulatory
Programmes
SG 6: Co-operation on Risk Assessment
SG 3: Testing a Representative
Set of Manufactured
Nanomaterials
SG 8: Exposure Measurement
and Exposure Mitigation
SG 4: Manufactured
Nanomaterials and Test
Guidelines
SG 7: The Role of Alternative
Methods in Nanotoxicology
SG 1/2: Database and Research Strategy(ies) on Human Health and
Environmental Safety Research
SG 5: Co-operation on Voluntary Schemes and Regulatory
Programmes
SG 6: Co-operation on Risk Assessment
Sub-groups who’s work provides a platform for coordinated (or not conflicting) authority action
(regulatory or voluntary), but where different
approaches are currently applied for chemicals in
general in OECD countries
6
Sub-groups who’s work provides the fundament for coordinated (or not conflicting) authority/industry action
(regulatory or voluntary)
Set of Manufactured
Nanomaterials
SG 4: Manufactured
Guidelines
Will finish Stage 1 exploratory
testing between 2010 and 2011
Set of Manufactured
Nanomaterials
Will finish phase 1 (occupational)
in the medium term
SG 4: Manufactured
Guidelines
Will finish evaluation of changes
needed between 2010 and 2011
7
4. EU Legislation – what’s next

Current legislation covers in principle the
relevant risks relating to nanomaterials.

In action, European Parliament have
followed this line in the recent co-decision
process for Novel Foods and Cosmetics
legislation, but nano-safety specific
requirements have been introduced
4. EU Legislation – REACH

REACH is based on the principle that M/I
and DUs have to ensure that they
manufacture, place on the market or use
such substances that do not adversely affect
human health or the environment.

REACH requirements apply to
nanomaterials, even though there are no
specific provisions for nanomaterials.
8

Definitions:

Nanomaterial
Substance at the nanoscale
Nano form vs. bulk form
Scope includes also e.g. agglomerates and
aggregates below/at micro size

Registration of substances manufactured/
imported in volumes of 1 tonne or more per year
Chemicals Safety Report required at volumes of 10
tonne or more per year
Tonnage triggers apply to the total volume
Safety has to be ensured for the substance in
whatever size or form and for manufacturing and
all identified uses.
A registration has to include all relevant
information on the nanomaterial.
9
4. EU Legislation – CLaP

Nanomaterials having specific properties may require a
different classification and labelling compared to the bulk
material, also when the nanoform is derived from a bulk
substance

Following CLP:

the information shall relate to forms or physical states in which
which the
substance is placed on market / used;
tests shall be carried out on the substance in the form(s)
form(s) or physical
state(s)
state(s) in which it is placed on the market and used.
4. EU Legislation – what’s next?
We need to work on Substance Identification
Substance identification of nanomaterials takes place
on the basis of:
-
-
‘traditional’
traditional’ parameters,
parameters, i.e. name of the substance,
information re molecular and structural formula,
composition of the subst
refinement based on specific parameters characterizing the
nanomaterial
properties of the substance allowing for meaningful sharing
of data
Build on OECD WPMN work!
10
We need to work on Chemical Safety Assessment

Guidance on Information requirements and Chemical
Safety Assessment (IR(IR-CSA TGD) is available from ECHA;
The guidance does not yet address specific characteristics
of nanomaterials;
The same assessment principles apply, but guidance needs
further work for use on nanomaterials.
SCENIHR opinion provides critical analysis
We need to work on Test Guidelines

In order to address the specific properties, hazards and
risks associated with nanomaterials, additional testing or
information may be required.

To determine specific hazards associated with
nanomaterials, current test guidelines may need to be
modified. Until specific test guidelines for nanomaterials
exist, testing will have to be carried out according to
already existing guidelines.
11
EP Resolution (up for adoption/rejection today):
3. Does not agree, before an appropriate evaluation of
current Community legislation, and in the absence
of any nano-specific provisions therein, with the
Commission's conclusions that a) current
legislation covers in principle the relevant risks
relating to nanomaterials, and b) that the
protection of health, safety and the environment
needs mostly be enhanced by improving
implementation of current legislation, when due to
the lack of appropriate data and methods to assess
the risks relating to nanomaterials it is effectively
unable to address their risks;
EP Resolution (up for adoption/rejection today):
3. Does not agree, before an appropriate evaluation of
current Community legislation, and in the absence
of any nano-specific provisions therein, with the
Commission's conclusions that a) current
legislation covers in principle the relevant risks
relating to nanomaterials, and b) that the
protection of health, safety and the environment
needs mostly be enhanced by improving
implementation of current legislation, when due to
the lack of appropriate data and methods to assess
the risks relating to nanomaterials it is effectively
unable to address their risks;
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5. Conclusions

The European Parliament is of the view that the time
for policy action (regulatory) has come
The Commission will carefully examine the
suggestions made by the European Parliament
The OECD WPMN is central to inform this discussion
in a (internationally) coherent way
Many scientific gaps still exist and need to be
addressed, but this will take time
The situation of having policy needs which can not
(yet) be answered by science is not new
If the policy needs increase, then further stepping up
of efforts on the (regulatory) science basis will prove
the more essential
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