Future Technologies Division 2 0 1 0 2 0 1 5 2 0 Future Technologies Division Dr. Wolfgang Luther Results of the European "NANOSAFE“-Project

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Future Technologies Division

Dr. Wolfgang Luther

Results of the European "NANOSAFE“-Project

page 2 / www.zt-consulting.de


• Starting point and facts on the project

• Aspects of Risk Assessment and Management

• Results

• Conclusion

• Outlook

Outline



Starting point of the project (2003)

InformationGap

Demand for a realisticrisk assessment andopen communication

• Many information on products/processes kept confidential

• Information available is widely spread throughout literature

• Understanding needs knowledge from a variety of disciplines (toxicology, chemistry, physics, epidemiology, law etc.)

Nanotech-Companies• Concerned with HSE apects

• Risks for workers, customersor future business?

Governments• Regulatory framework for NT

• Misdirected Nanotechinvestments ?

? ??Public/ Media• Increasing reporting on nano-risks

• Nano-Moratorium ?



Lack of Data for Risk AssessmentEmission paths and volume

• Broad range of potential applications• Confidentiality of production processes and products• Particle release during use and disposal

Effects in human body/environment• Toxicological mechanisms• Entry, deaggregation and distribution in the human body • Transport, persistence and acumulation in the environment

Measurement techniques• Workplace measurement, biological samples• Relevant metrics for risk assessment & determination• Standardization

Potential

Risks ?

?

?

?

Risk Management• Personal protective measures for workers• Regulatory framework (chemicals, air quality, cosmetics, food, drugs)



Nanosafe project - Some Facts

• Official Title: „Risk Assessment in Production and Use of Nanoparticles

with Development of Preventive Measures and Practice Codes“

• Funded by the European Commission within the Competitive and Sustain-

able Growth (GROWTH) programme of the 5th framework programme

• International interdisciplinary consortium of experts

• Duration of the Project: April 2003 to July 2004 (15 months)

• Methods: data base searches, literature analysis and interviews



Project Partners

Co-ordinator:Nanogate Technologies GmbH, NT (D)

Contractors:• Commissariat a L'Energie Atomique, CEA (F)• VTT Technical Research Centre of Finland (FIN)• University of Oxford, Department of Engineering Science, (UK)• Oxonica Limited, Oxford (UK)• Jozef Stefan Institute, (Sl)• Katholieke Universiteit Leuven (B)• GSF-Forschungszentrum für Umwelt und Gesundheit GmbH, (D)• VDI Technologiezentrum GmbH, VDI-TZ (D)



Particle Characteristics• Aspect-ratio• Diameter (particle/aggregate)• Surface area/ properties• Water solubility• Chemical composition

Emission• Production volume• Potential particle release (production, use, disposal)

Health effects• Humans• Experimental animals

Environmental effects• Persistence• Biomagnification• Long range transport

1 Hazard Identification 2 Hazard CharacterizationEpidemiological Studies• Workers• Consumers• Exposed population

In vivo studies• acute/chronic• different species

In vitro studies• Human/ animal, different cell types• Models (lung, skin, systemic)

Exposure routes• Inhalation, dermal, ingestion

Environmental monitoring• Biological uptake ...

Occupational monitoring• Personal exposure

3 Exposure Assessment

4 Risk CalculationSusceptibility extrapolation models• high dose low dose• animal human

Threshold value calculation• Intake, immission conc., maximum workplace conc.

6 Risk ManagementPreventive Measures• Personal protection equip.• Modification of processes

Regulation• Exposure/ immission stand. • Production restrictions

6 Steps of Risk Assessment and Management

5 Risk Communication

Regulatory bodies, industry

Science, Public, Consumers



Working Groups

• WG 1: Types of nanomaterials, manufacturing and handling procedures Group Leader: VTT, Pertti Lintunen

• WG 2: Applications, industrial and consumer Group Leader: NT, Ulrike Dellwo

• WG 3: Potential particle release, circumstances and conditions Group Leader: CEA, Frédéric Schuster

• WG 4: Danger to health, reaction mechanism with human organism Group Leader: KUL, Peter Hoet

• WG 5: Recommended preventive measures Group Leader: GSF, Irene Brueske-Hohlfeld

• WG 6: Standards and regulatory recommendations Group Leader: VDI-TZ, Wolfgang Luther



ResultsTypes of nanomaterials and manufacturing

Dispersion in• gases (aerosols)• liquids (e.g. gels, ferrofluids)• solids (e.g. matrix materials)

Shape/Structure• spheres• needles, tubes• platelets

NanoparticulateMaterials

UltrafineAerosols

Quantumdots

Nano-particles

Nano-tubes

Nano-capsules

Origin• natural• unintentionally released• manufactured („old“, „new“)

Aggregation state• single particles• aggregates• agglomerates

Surface modification• untreated • coated • core/shell particles

Manufacturing• gas phase• liquid phase • mechanical procedures

Chem. composition• metals/ metal oxides• polymers, carbon• biomolecules



ResultsApplications

Form of Application• Fixed in a solid matrix• Dispersed in liquids, slurries ... • Dry powders• Closed systems• Open application ...

Types of Products• Intermediates

– Fillers, coatings ...• End user products

– electronics, medicine,

food, cosmetics ...

Production Volume• laboratory scale (< 1 t p.a. quantum dots)• semitechnical-scale (CNT)• Industrial scale (> KT p.a. carbon black, aerosil, titania...)



ResultsExposure to Nanoparticles

Source: Royal Society

WorkersTake in mind: Exposure from con-ventional processes:• Smelting, soldering• Dusts and sprays

Consumers• Cosmetics, Drugs

Take in mind: Exposure of popula-tion from unintentio-nally released nano-particles and natural aerosols• Diesel exhaust !



ResultsPotential Particle Release during Manufacturing

• Most of processes in an inert atmosphere or in vacuum, relatively safe except in case on unexpected failures during the processing (e.g.chamber failures causing leakages).

• Leakages are risk especially at high pressure conditions (e.g. supercritical fluids)

• Collecting apparatus of nanoparticles must be able to stop the particles efficiently (filters, electrostatic devices, substrate plates, suspensions)

• Particle release is more likely to happen after the production process

– During handling, treatment or bagging of nanoparticles

– During cleaning procedures of the equipment

Source: CEA

In most cases:

Aggregates of

nanoparticles



ResultsPotential Entry Routes into the Human Body

Source: Encarta Enzyklopädie Standard 2003, Microsoft Corporation

Potential Health Effects• Lung: Inhalation of solid (poorly soluble)

material– Biopersistence & Cancer risk– Systemic translocation of particles– Thrombosis and lung inflammation

• Intestinal tract: No evidence for uptake of

nanoparticles, except drugs

• Skin:– Translocation of particles from topical exposure– Mechanical skin irritation



Particles in the nanosize range can certainly enter the human body via the lungs

and the intestines; penetration via the skin is less evident although strong evidence

exists that some known particles can penetrate deep into the dermis.

The penetration is depending on the size and surface properties of the particles

and also depends on the point of contact in the lung, intestines or skin

The distribution in the body is strongly depending on the surface characteristics of

the particle.

There is no universal ”nanoparticle” to fit all the cases, each nanomaterial should

be treated individually when health risks are expected.

The health risks of inhaled fibrous material needs to be examined with care,

because it is general accepted that fibres that are not cleared easily from the lungs

can induce pulmonary disease.

ResultsToxicological Assessment



ResultsPreventive Measures for workers

• Process modification

• Isolation of process

• Local exhaust ventilation

• Work practices

• Personal protective

equipment (respirators,

masks, gloves ...)

• Safety data sheets



• Immission Control

• Chemicals

• Labor protection

• Pharmaceutical and medicine

• Food, consumer goods and cosmetics

• Novel-Food

ResultsLegislation Framework - Areas to be Considered



Area of interest Regulation and Safety Measures

Drugs Drug Approval Application ProcessFood Impose Conditions for manufacturing processeses

Obligations for indication and permission of producing and selling Prohibitions labelling and warning notices

Consumerproducts andcosmetics

Product safety standards Establish obligations for the indication and permission of

producing and selling

Air pollution Limit values for emission and immission

Worker Safety Exposure limits Safety standards and guidelines

Hazardoussubstances andchemicals

Registration of substances/chemicals (e.g. CAS) Guidelines for handling of hazardous substances

ResultsOptional regulation measures



ResultsRegulation Activities

Worker Safety • Regulation relies on limit values for hazardous chemicals (e.g. WHO or MAK)

• dependent on the availability of measurement techniques, existing standards for based on mass concentrations, not applicable to ultrafine aerosols

Consumer Protection • So far no regulations for nanoparticle exist or are planned for the near future,

• Material producers will be responsible for the assessment of health risks associated with their products

Chemical Legislation • Also in the frame of chemical legislation particle size does not play a role for the registration of new substances

• European Chemical Policy (Reach) will already create bottleneck of assessing

30000 „old“ substances Urgent need for preliminay risk assessment scheme to prioritize work



Productionvolume• < 10 kg• < 1 t p.a.

ToxicologicalScreeningLung toxicitySystemic effectsOxidative stressorEndocrine disruptorSensitiser/Adjuvant

EcotoxicologicalScreeningPersistenceLong rangeTransportationBiomagnification

Scheme for Preliminary Risk Assessment ofNanoparticles

Aerosolrelease ProductionHandlingProcessing

Directexposure CustomersWorkersEnvironment

ParticlepropertiesSolubilityAspect RatioDiameterSurface

Increasing investigation expenditures

Intermediate priorityLow priority High priority

Find suitable parameters for prioritize investigations !



• R&D-Projects and Data Collection (Development of methods and screening tests, data collection on workplace exposure and nanoparticle behaviour in the human body and the environment)

• Minimizing risks (protection equipment, process modification)

• International Standardisation (methods, guidelines, etc.)

• International cooperation and initiatives

• Regulation should be considered on basis of existing legislation

• Risk Communication (two-way process)

Some General Recommendations



• Several Research Projects are going to start soon in Germany (Nanocare), Europe (Nanosafe II) and the U.S.

• Nanotechnology is on the agenda of standardization and regulation bodies

• Generate more data as a basis for a matter of fact oriented discussion

Outlook

Documents

Future Technologies Division 2 0 1 0 2 0 1 5 2 0 Future Technologies Division Dr. Wolfgang Luther Results of the European "NANOSAFE“-Project