Scientific Committee on Emerging and Newly-Identified Health Risks SCENIHR OPINION ON THE APPROPRIATENESS OF THE RISK ASSESSMENT METHODOLOGY IN ACCORDANCE WITH THE TECHNICAL GUIDANCE DOCUMENTS FOR NEW AND EXISTING SUBSTANCES FOR ASSESSING THE RISKS OF NANOMATERIALS

................................................................................................... 4 EXECUTIVE SUMMARY..................................................................................... 8 1. BACKGROUND....................................................................................... 11 2. TERMS OF REFERENCE ........................................................................... 11 3. SCIENTIFIC RATIONALE ......................................................................... 12 3.1. General introduction ...................................................................... 12 3.2. Physicochemical properties relevant for hazard characterisation of nanoparticles ....................................................................................... 13 3.2.1. Special characteristics of nanoparticles.................................. 13 3.2.2. General principles for approaching nanoparticle characterisation14 3.3. Exposure assessment of nanomaterials............................................. 14 3.3.1. Exposure assessment algorithm ........................................... 14 3.3.1.1. Explanation of Terms in Figure 1 ............................. 15 3.3.1.2. Steps in the Exposure Assessment Algorithm ............ 16 3.3.1.3. Routes of Exposure ............................................... 17 3.3.2. Exposure control measures.................................................. 18 3.3.2.1. Containment ........................................................ 18 3.3.2.2. Local Exhaust Ventilation (LEV)............................... 18 3.3.2.3. Filtration.............................................................. 18 3.3.2.4. Personal protective equipment ................................ 19 3.3.3. Exposure assessment for the environment............................. 19 3.4. Effects assessment of nanomaterials ................................................ 20 3.4.1. General approach............................................................... 20 3.4.2. Toxicokinetics.................................................................... 20 3.4.2.1. Absorption ........................................................... 20 3.4.2.2. Distribution.......................................................... 21 3.4.2.3. Metabolism .......................................................... 22 3.4.2.4. Excretion ............................................................. 22 3.4.3. Toxicity 22 3.4.3.1. Reproductive toxicity/ Teratogenity : ....................... 22 3.4.3.2. Immunotoxicity .................................................... 23 The appropriateness of the risk assessment methodology in accordance with the Technical Guidance Documents for new and existing substances for assessing the risks of nanomaterials 6 3.4.3.3. Neurotoxicity........................................................ 23 3.4.3.4. Mutagenicity and Genotoxicity ................................ 23 3.4.3.5. Carcinogenicity..................................................... 24 3.4.3.6. Diseased lungs and susceptibility to the effects of nanoparticle ......................................................... 24 3.4.4. Ecotoxicology .................................................................... 25 3.5. Risk characterisation of nanomaterials.............................................. 26 3.5.1. The difference between nanoparticles and bulk chemicals ........ 26 3.5.2. Potential risks to human health ............................................ 27 3.5.3. Potential risks to the environment ........................................ 27 3.6. Measurement methods for characterisation, exposure and effects assessment .................................................................................. 28 3.6.1. Methods for the characterisation of nanoparticles ................... 28 3.6.2. Measurement methods for exposure monitoring ..................... 29 3.6.3. Methods for effects assessment for human health................... 30 3.6.3.1. In vivo studies...................................................... 30 3.6.3.2. Instillation v inhalation .......................................... 31 3.6.3.3. In vitro studies ..................................................... 32 4. OPINION .............................................................................................. 33 4.1. Chapter 2 Human Health ................................................................ 33 4.1.1. General Introduction (Section 1) .......................................... 33 4.1.2. Exposure Assessment (Section 2)......................................... 34 4.1.2.1. Workplace exposure .............................................. 35 4.1.2.2. Consumer exposure assessment ............................. 36 4.1.3. Effects Assessment (Section 3) ............................................ 38 4.1.3.1. Evaluation of data (Section 3.2).............................. 39 4.1.3.2. Dose-response assessment .................................... 40 4.1.3.3. Toxicokinetics....................................................... 40 4.1.3.4. Acute toxicity (Section 3.5) .................................... 40 4.1.3.5. Irritation and corrosivity (Section 3.6) ..................... 41 4.1.3.6. Sensitisation (Section 3.7) .................................... 41 4.1.3.7. Repeated dose toxicity (Section 3.8)....................... 41 4.1.3.8. Mutagenicity (Section 3.10 )................................... 42 4.1.3.9. Carcinogenicity (Section 3.11 ) ............................... 43 4.1.3.10. Reproductive toxicity (Section 3.12) ....................... 44 4.1.4. Risk characterisation (Section 4) .......................................... 44 4.2. Chapter 3 Environment .................................................................. 44 4.2.1. Section 1 General Introduction............................................. 44 4.2.2. Environmental exposure assessment (Section 2) .................... 45 The appropriateness of the risk assessment methodology in accordance with the Technical Guidance Documents for new and existing substances for assessing the risks of nanomaterials 7 4.2.3. Effect assessment (Section 3).............................................. 47 4.2.4. Bioavailability .................................................................... 48 4.2.5. Bioconcentration and bioaccumulation................................... 49 4.2.6. Environmental risk assessment (Section 4)............................ 49 4.3. Conclusions and Recommendations .................................................. 51 4.3.1. Conclusions on Human Health Chapter .................................. 51 4.3.2. Conclusions on the Environment Chapter............................... 52 4.3.3. A staged approach to the assessment of the human and environmental risks from nanomaterials. ............................... 53 4.3.4. Answers to specific questions asked from SCENIHR................. 59 5. MINORITY OPINION ............................................................................... 61 6. LIST OF ABBREVIATIONS........................................................................ 62 7. REFERENCES ........................................................................................ 63 The appropriateness of the risk assessment methodology in accordance with the Technical Guidance Documents for new and existing substances for assessing the risks of nanomaterials