ISO/TR TECHNICAL REPORT 16196 First edition 2016-10-01 Nanotechnologies Compilation and description of sample preparation and dosing methods for engineered and manufactured nanomaterials Nanotechnologies - Compilation et description de la préparation des échantillons et des méthodes de dosage pour les nanomatériaux d'ingénierie et manufacturés Reference number ISO/TR 16196:2016(E) ISO International Organization for Standardization @IS02016 ted without license from IHS IS0/TR 16196:2016(E) COPYRIGHT PROTECTEDDOCUMENT IS0 2016, Published in Switzerland All rights reserved. Unless otherwise specified, 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 Ch. de Blandonnet 8 . CP 401 CH-1214 Vernier, Geneva, Switzerland Tel. +41 22 749 01 11 Fax +41 22 749 09 47 [email protected] www.iso.org HS und networking permited without license from IHS IS0/TR 16196:2016(E) Contents Page Foreword ..V Introduction. ..vi 1 Scope. ..1 2 Normative references 3 Terms and definitions ..1 4 Abbreviated terms ..3 5 Background .3 5.1 Discussion of the importance of sample preparation and dosing 3 5.2 Discussion of specific issues when testing the toxicology of manufactured nanomaterials 4 5.2.1 Physical properties 4 5.2.2 Sample preparation. .4 5.2.3 Administration of doses ..5 5.2.4 Discussion of relationship between this document and IS0/TR 13014 ..5 5.3 Discussion of relevant dosing for toxicological screening. 5 5.4 Discussion of the relationship between this document and IS0/TR 16197 5.5 Review of other relevant international activities and documents ..5 6 Physico-chemical properties .6 6.1 Particle size, shape, size distribution and degree of agglomeration. .6 6.2 Chemical description Composition and identification. .6 6.3 Specific surface area. ..6 6.4 Surfacechemistry. .6 6.5 Isoelectric point, zeta potential and Hamaker constant .7 6.6 Influence of water chemistry on nanomaterial properties and dispersion behavior ..8 6.7 Preparation of liquid dispersions .8 6.8 Crystal structure 6.9 Surface energy or interfacial tension .8 6.10 Solubility .8 7 Considerations for preparing samples of nanomaterials in exposure media in ecotoxicity studies 9 7.1 General .9 7.1.1 Introduction to existing knowledge .9 7.1.2 Environmental behaviour .9 7.1.3 Degradation and transformation .9 7.1.4 Bioaccumulation .9 7.2 Test method applicability and dosimetry .10 7.2.1 Environmental distribution. .10 7.2.2 Degradation and transformation 10 7.2.3 Bioaccumulation .11 8 Methods for preparing nanomaterials for toxicological studies in mammals that ensure correct dosing .11 8.1 Issues to consider for stock dispersion preparation .11 8.2 Importance of monitoring stability of test dispersions during experiments. .11 8.3 Special considerations for physiological salines used in mammalian studies 12 8.4 Routes of delivery and behaviour of nanomaterial dispersions in mammalian studies... 12 8.4.1 Respiratory tract exposures. 12 8.4.2 Oral exposure. .12 8.4.3 Dermal exposures. ..13 8.4.4 Injection routes .13 9 Methods for preparing samples of nanomaterials for use in cell cultures ..13 9.1 Cell cultures and dispersion of nanomaterials in culture media ..13 9.1.1 General. .13 ii