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Nanomaterial - human health risk assessment -

Nanomaterial - human health risk assessment -

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Nanomaterial - human health risk assessment -

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  1. Nanomaterial- human health risk assessment - Maria Wallén, toxicologist Reach Department Swedish Chemicals Agency (Kemikalieinspektionen) ____________________ Biomaterials Research Center, Gothenburg´s university Nov 13, 2008

  2. Risk assessment in general • Risk assessment and nanomaterials • Definition of nanomaterial • Issues to be considered in testing • Legislation (REACH regulation) • Nanomaterials in products • Nanomaterials and human exposure • Nanomaterials and human toxicity

  3. Human health risk assessment of chemicals Information on Exposure Phys/chem prop Toxicokinetics Effects • Exposure assessment • Exposed populations • Exposure patterns • Effects assessment • Hazard identification • Dose/response Exposurehumans NOAELanimals Extrapolate experimental animal data to human situation Riskcharacterisation Exposure level / Effect level Risk management

  4. Human health risk assessment of nanomaterials Do we need to study nanomaterials differently compared to bulk chemicals? ? To be investigated!

  5. Phys/chem properties • Large surface area per volume • High reactivity • Size and shape • 1 - 100 nanometer Unique optical, electrical and magnetic properties Quantum effects Definition • Intentionally formed • Unintentionally formed • Natural occurrance C60-fullerene ? To be agreed! SWCNT

  6. Issues to be considered in the risk assessment of nanomaterials (1) • Exposure • What are the relevant exposure metrics? • Which data can be reliably collected? • Analytical methodologies • Effects of adsorption and aggregation • Measurement strategies • How should uncertainty of data be handled?

  7. Issues to be considered in the risk assessment of nanomaterials (2) • Physical-chemical properties • Aggregation (nanomaterial – nanomaterial interaction) • Water solubility (nanomaterial held in a colloidal suspension) • Shape • Particle size distribution • Specific surface area • Surface chemistry

  8. Issues to be considered in the risk assessment of nanomaterials (3) • Toxicokinetics – ADME (Absorption, Distribution, Metabolism, Elimination) • The small particle size • The shape and surface composition • Aggregation may produce particles too large for absorption • Interaction with molecules (proteins, lipids, salts, etc) in the biological environment leading e.g. to extensive tissue retention

  9. Issues to be considered in the risk assessment of nanomaterials (4) • Effect endpoints • Endpoints for testing • Testing methods • Sample preparation and dosimetry • How to prepare the dosing material • How to administer dosing material for tox. test • Estimating dose • Deposition of small materials?

  10. OECD; Environment DirectorateWorking Party on Manufactured Nanomaterials (WPMN) • Exposure measurement and assessment • Investigate the possible use of current OECD test guidelines • The role of alternative (non in vivo) test methods • Risk assessment • Safety testing of a representative set of manufactured nanomaterials (Sponsorship programme)

  11. Sponsorship Arrangement (OECD) • To agree on a list of representative manufactured nanomaterials • To develop a programme to test nanomaterials for human health and environmental safety


  13. How do REACH apply to nanomaterials? ? To be considered! LegislationREACH Regulation (EC) No 1907/2006Registation, Evaluation, Authorisation and Restriction of Chemicals ”REACH covers nanomaterials” (EU Commission)

  14. Issues to be considered in the REACH regulation and nanomaterials (examples) • Obligation to register substances (Article 6, 7) • Requirements for Safety Data Sheets (SDS) (Article 31)

  15. Obligation to register • Any manufacturer or importer of a substance in quantities of one tonne or more per year shall submit a registration to the Agency. • Any producer or importer of articles shall submit a registration to the Agency, if • the substance is present in articles in quantities over one tonne per producer or importer per year…..

  16. Safety Data Sheets (SDS) • The supplier of a substance shall provide the recipient of the substance with a safety data sheet if • the substance meets the criteria for classification as dangerous (CMR); or • the substance meets the criteria as persistent, bioaccumulative and toxic (PBT) …., or • … an equivalent level of concern… (eg endocrine disrupters)

  17. Reach Competent Authorities subgroup on Nanomaterials (Reach CASG Nano) 2008-2012 • Definition of nanomaterials • Registration • Chemical Safety Assessment • Classification and labelling • Testing methods inclusive alternative methods • Safety data sheet (SDS) • Authorisation and Restrictions • Guidance


  19. Nanomaterials in products (examples) • Electronics • Househould products • Clothes and textiles • Sport items • Automobiles • Toys • Hygiene articles • Cosmetic products • Food and food additives • Pharmaceuticals

  20. Toxicity of nanomaterials Are nanomaterials toxic to human health? ? Knowledge is limited

  21. Exposure to humans - workers, consumers, man via the environment - • Uptake via • The lungs, the oral route, the skin, the olfactory nerve to the brain • Passage via • Blood-brain barrier • Cell membranes into mitochondria and cell nucleus • Localised to • e.g. liver, spleen, lymph nodes, bone marrow, brain

  22. Effects on the lungs (1) • Size • high amount in the lungs of nanosized particles (TiO2 and Al2O3) compared to larger particles of the same substances  greater pulmonary inflammatory response (rats, mice) • Shape • high amount in the lungs of nanotubes (15-20 µm; SWCNT) compared to nanoparticles (quantum dots )  greater inflammatory response (often discussed in relation to asbestosis) (rats)

  23. Effects on the lungs (2) • Surface area • Nanoparticles with greater surface area were more cytotoxic than larger particles of equivalent mass (SiO2) (in vitro)  might explain pulmonary fibrosis

  24. Effects on the cardiovascular system • Air pollution (nanosized particles) • cause oxidative stress (rats; inhalation)  may lead to inflammation and myocardial cell injuries • SWCNT respiratory exposure • Induces oxidative stress and injuries in the vessel cells (mice; instilled in the lungs)  might lead to cardio-vascular diseases such as artherosclerosis • Nanoparticles • can modify blood clotting factors (mice; ip) may lead to thrombosis

  25. Effects on the nervous system • Positively charged nanoparticles (emulsifying wax) have toxic effect at the blood-brain barrier (rats; in situ brain perfusion) disturbances of the BBB may lead to modified toxicity for nanosized material and chemicals in general

  26. Very limited knowledge • Effects on the skin • Effects on the reproductive system and foetuses • Mutagenicity • Cancer • Effects on the immune system

  27. Finally, • We need advise how to deal with nanomaterials in the legislation • There are large uncertainties and limited knowledge on human health risks of nanomaterials • There is a need to understand how to assess exposure to nanomaterials • There is a need to establish adequate testing methods to evaluate the toxicity of nanomaterials • There are problems to communicate possible risks caused by nanomaterials.

  28. KemI Report 3/08Kemi Rapport 6/07 (sv) NanotechnologyHigh risks with small particles A compilation of available knowledge concerning risks for health and environment from nanotechnology, and proposals on measures for how to fill the identified knowledge gaps Thank you for your attention!