ISO/TR TECHNICAL REPORT 22019 First edition 2019-05 Nanotechnologies Considerations for performing toxicokinetic studies with nanomaterials Nanotechnologies - Considérations pour realiser des études toxico cinétiques de nanomatériaux Reference number ISO/TR22019:2019(E) @ IS0 2019 IS0/TR22019:2019(E) COPYRIGHTPROTECTEDDOCUMENT @ IS0 2019 All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting on the internet or an intranet, without prior written permission. Permission can be requested from either IsO at the address below or Iso's member body in the country of the requester. ISO copyright office CP 401 : Ch. de Blandonnet 8 CH-1214 Vernier, Geneva Phone: +41 22 749 01 11 Fax: +41 22 749 09 47 Email: [email protected] Website: www.iso.org Published in Switzerland ii @ IS0 2019 - All rights reserved IS0/TR 22019:2019(E) Contents Page Foreword .iv Introduction 1 Scope. 1 2 Normative references 1 3 Terms and definitions 1 4 Abbreviations .3 5 Importance of toxicokinetic information for risk assessment of nanomaterials .3 5.1 General 3 5.2 Possible use of toxicokinetic information. 4 5.3 Key toxicokinetic issues for nanomaterials. .5 6 Factors influencing the toxicokinetics of nanomaterials 5 6.1 Dissolution rate 5 6.2 Physical chemical properties determinant for toxicokinetic behavior 6 7 Analytical challenges 10 7.1 General 10 7.2 Analysis of element 10 7.3 Analysis of element radiolabel or fluorescence label 11 7.4 Determination of particles. 12 7.5 Limit of detection 13 8 Issues relevant for dosing conditions 13 8.1 General 13 8.2 Dosemetrics 14 9 Absorption of nanomaterials 15 9.1 General 15 9.2 Skin. 15 9.3 Gastrointestinal (GI) tract 16 9.4 Respiratory tract 18 10 Distribution .22 10.1 General 22 10.2 Organ distribution 22 10.3 Transport across the placenta, BBB and to reproductive organs .23 11 Metabolism/degradation .24 12 Excretion .24 13 Conclusions .25 Annex A (informative) Definitions as used in OECD Test Guideline 417:2010 .29 Annex B (informative) Quantitation methods for nanomaterials, advantages and challenges .32 Bibliography .39 @ IS0 2019 - All rights reserved iii