1. the SAFETY assessment of nanomaterials

2. About this talk This talk will describe:
The value of harmonised test guidelines for chemicals for use in hazard identification and risk assessment;
The role of OECD’s test guidelines programme and the benefits for both governments and industry in using OECD test guidelines;
It will cover the process by which many test guidelines were found to be suitable for nanomaterials;
Not all test guidelines are suitable for nanomaterials and it should with the example of inhalation toxicity how new nano specifc approaches have been developed.

3. Mutual Acceptance of Data, Test Guidelines and Good Laboratory Practices

4. Mutual Acceptance of Data (MAD)
Good Laboratory
Practice
Test
Guidelines
Recommendation on the Safety Testing and Assessment of MN
A single quality standard should be applied for testing of all chemical substances
A single quality standard for test facilities throughout OECD
Mutual Acceptance of Data
Legally binding on OECD Member countries
and other MAD Adherents
“data generated in the testing of chemicals in an OECD Member country in accordance with OECD Test Guidelines and OECD Principles of Good Laboratory Practice shall be accepted in other Member countries for purposes of assessment and other uses relating to the protection of man and the environment”
DATA QUALITY ENSURED BY TG and GLP
Test Guidelines:
Approximately 150 Test Guidelines to determine the safety of chemicals and chemical preparations, including pesticides and industrial chemicals.
Physical-chemical properties
Human toxicity
Ecotoxicity
Bio-degradation and accumulation
Pesticide residue testing
Good Laboratory Practice:
Testing facility’s organisation and personnel, quality assurance programme, physical plant, apparatus, materials and reagents.
In order to govern principles, testing facilities should provide;
conditions for establishing and maintaining test systems;
standard operating procedures;
performance of the study;
reporting of results;
storage, retention and retrieval of records and materials etc.
Full Adherents to MAD
South Africa (since 2003)
Singapore (since 2010)
India (since 2011)
Brazil (since 2011)
Argentina (since 2011)
Malaysia
Provisional Adherent : Thailand
→Avoids duplication of testing: around Euros 150 million saved each year
→Reduces use of animals
→Reduces trade barriers

5. C(81)30 Council Decision on MAD
Country A Lab Chronic Tox Test Results
Country B regulator
Country C regulator
Country D regulator
Country B Lab Aquatic Tox Test Results
Country A regulator
Note: key aspects are “no repeat testing” and interpretation of test results is government prerogative

6. BY AVOIDING DUPLICATIVE TESTING:
SAVINGS FROM MAD
BY AVOIDING DUPLICATIVE TESTING:
At least € 150 Million / Year
Reduction in animal testing
More chemicals can be evaluated quicker
1998 study

7. Approximately 150 Test Guidelines:
Section 1: Physical Chemical Properties
Section 2: Effects on Biotic Systems 
Section 3: Degradation and Accumulation
Section 4: Health Effects 
Section 5: Other Test Guidelines (i.e. Pesticides residues)
Every year new and updated Test Guidelines are adopted to meet the regulatory needs in OECD member countries.
Toxicological evaluation and the processes…

8. Difference between OECD Test Guidelines and Guidance Documents.
Test Guideline
Regulatory need explained by the SPSF*
Covered by MAD
Fixed test protocol with validity criteria
Thorough experimental validation needed with fixed protocol
Takes time and resources and more cumbersome to update
Guidance Document
Regulatory need
Not covered by MAD
Can be a test method, or it provides technical guidance for the use of test guidelines
Scientific validation could be limited and based on published literature
Faster to develop and revise

9. China Lead sponsor(s) Co-sponsor(s) Contributor Fullerenes(C60)
Japan, US
  China
SWCNTs
Germany, Canada, EC, France,  China
MWCNTs
Korea, BIAC
Silver nanoparticles
US, Korea
Germany, Canada
Australia, EC, France,  China
Iron nanoparticles
 China
Canada, US
Carbon black
Germany, US
Titanium dioxide
Germany
Canada, Spain, BIAC, Korea, US
France,  China
Aluminium oxide
Cerium oxide
UK/BIAC, US
Netherlands,
Australia, Germany, EC
Zinc oxide
UK/BIAC
BIAC
Australia, Canada,
Silicon dioxide
 BIAC, Korea
EC, France
Polystyrene
 Korea
Dendrimers
Spain US
Nanoclays
Note:
- Countries with * have stated a clear interest
- Countries in (brackets) have stated a clear interest but have yet to confirm their exact role, i.e., whether they will be sponsors, co-sponsors or contributors
- # TiO2 is Spain’s initial choice but they may consider proposals for selecting other metal containing nanomaterial

10.
Testing Programme Overview
Dossiers and Endpoints ‌
Learn more about the Programme.
Overview
Download Manufactured Nanomaterials Dossiers or search for Tested Endpoints.
Downloads and searches
Sponsors
More information
Learn more about our sponsoring countries and institutions.
Request additional information about the Programme.
Contact
SPSF = Description of the project including e.g. regulatory requirements, timelines, validation status and needs, resources involved in a project
Essential Criteria to be met before considering a proposal:
Regulatory need/Data requirement
Contributes to the International Harmonisation of Hazard/ Risk Assessment
Addresses a health or environmental concern
Considerable support from Member countries
Lead country/Stakeholder identified

11. Process for Project proposals (SPSF) for the Test Guidelines Programme
New and updated Test Guidelines are developed to:
Meet regulatory needs of member countries
Reflect scientific progress
Address animal welfare aspects
Improve cost-effectiveness of test methods
Standard Project Submission Form (SPSF)
Submission: November for discussion at the following WNT Meeting
SPSF = Description of the project including e.g. regulatory requirements, timelines, validation status and needs, resources involved in a project
Essential Criteria to be met before considering a proposal:
Regulatory need/Data requirement
Contributes to the International Harmonisation of Hazard/ Risk Assessment
Addresses a health or environmental concern
Considerable support from Member countries
Lead country/Stakeholder identified

13. NANOSAFETY

14. Test Guidelines/ Guidance Documents under preparation
Amendments to the Inhalation TGs and GD to Accommodate NM
GD on Aquatic (and Sediment) Toxicology Testing of NM
GD for Dispersion and Dissolution of NM in Aquatic Media – Decision Tree
GD on Assessing the Apparent Accumulation Potential of NM
TG for Dispersibility and Dispersion Behaviour of NM in Aquatic Media
(new) TG for NMs Removal from Wastewater
GD on the Adaptation of In Vitro Mammalian Cell Based Genotoxicity TGs for Testing of MNs
New SPSF under development - review TG Particle Size Distribution/Fibre Length and Diameter Distributions

15. An example: Relationship to the test guidelines on dispersion stability and dissolution rate of nanomaterials in aqueous media
GD on dissolution rate and dispersion stability of nanomaterials for environmental risk assessment
TG 318 on dispersion stability in simulated environmental media
(published)
TG on dissolution rate in aquatic media
(1 draft April 2017)
Explanations and recommendations for a (jointly) consideration of testing, interpreting and usage of data on both dissolution rate and dispersion stability of NMs
©IUTA

16. What is Needed Session 1: Physical Chemical Properties
TG Water Solubility – Specific Modification Suggested
TG Complex Formation Ability in Water (Polarographic Method)
TG Density of Liquids and Solids
TG Dissociation Constants in Water
TG Surface Tension of Aqueous Solutions
Session 4: Health Effects
TG 428 Skin Absorption: In Vitro Method
TG 431 In vitro skin corrosion: reconstructed human epidermis (RHE) test method
TG 437 Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants

17. What is Needed Session 2: Effects On Biotic Systems
TG Freshwater Alga and Cyanobacteria, Growth Inhibition Test
TG Daphnia sp. Acute Immobilisation Test
TG Fish, Early-life Stage Toxicity Test
TG Soil Microorganisms: Nitrogen Transformation Test
TG Soil Microorganisms: Carbon Transformation Test
TG Enchytraeid Reproduction Test
TG Earthworm Reproduction Test (Eisenia fetida/Eisenia andrei)
TG Sediment-Water Lumbriculus Toxicity Test Using Spiked Sediment
A. Kerstin Hund-Rinke, Anders Baun, Denisa Cupi, Teresa F. Fernandes, Richard Handy, John H. Kinross, José M. Navas, Willie Peijnenburg, Karsten Schlich, Benjamin J. Shaw & Janeck J. Scott-Fordsmand (2016): Regulatory ecotoxicity testing of nanomaterials – proposed modifications of OECD test guidelines based on laboratory experience with silver and titanium dioxide nanoparticles, Nanotoxicology, DOI: /

18. Status of Revisions on Inhalation
The amended TGs 412 and 413 are finalised published at the end of October – First TGs amended for NM!
The amendments concern:
Bronchoalveolar lavage (BAL) measurements;
Particle-Size Distribution For Test Atmospheres;
Post-Administration Duration; and
Lung Burden Measurements.

19. TG 318- Dispersion behaviour of NMs in different environmental media
This new TG is finalised and published – First TGs for NM!
This TG aims to determine the dispersion stability of NM in aqueous media in dependence of environmental conditions.

20. NEW PROPOSALS (Agreed, February 2018)
Determination of solubility and dissolution rate of nanomaterials in water and relevant synthetic biologically mediums
Identification and quantification of the surface chemistry and coatings on nano- and microscale materials
Determination of the Dustiness of Manufactured Nanomaterials
Applicability of the TG 442D in vitro skin sensitisation for nanomaterials
Aquatic (Environmental) Transformation of Nanomaterials
Development of new Test Guideline on Toxicokinetics or Amendments to OECD TG 417 to accommodate NM
Assessment of the durability of nanomaterials and their surface ligands in environmental surroundings

21. Manufactured Nanomaterials
Thank you!
Safety of
Manufactured Nanomaterials