ISO/TR TECHNICAL REPORT 10993-33 First edition 2015-03-01 Biological evaluation of medical devices - Part 33: Guidance on tests to evaluate genotoxicity Supplement to Iso 10993-3 Evaluation biologique des dispositifs médicaux- Partie33:Directives sur les essais pour évaluer lagenotoxicité- Supplement al's0 10993-3 Referencenumber IS0/TR10993-33:2015(E) LSO Intemational Organization for Standardization @IS02015 ed without license from IHS IS0/TR10993-33:2015(E) COPYRIGHTPROTECTEDDOCUMENT ISO2015 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 Case postale 56.CH-1211 Geneva 20 Tel. +4122 749 0111 Fax +41 22 749 09 47 E-mail copyright@iso.org Web www.iso.org Published in Switzerland PrganizationforStandardization networking permited without license from IHS NotforResale, 2015/6/207:12:11 IS0/TR10993-33:2015(E) Contents Page Foreword ..vi Introduction.. .viii 1 Scope. 2 Selection oftests 3 Recommendedtests ..1 4 Use of invitro teststo detect genotoxicity 5 Use of in vivo tests to detect genotoxicity ..2 6 Bacterialreversemutationassay .3 6.1 General .3 6.2 Preparations .3 6.2.1 Bacteria .3 6.2.2 Medium ..4 6.2.3 Metabolic activation 4 6.2.4 Test samplepreparation ..4 6.3 Test conditions.. 4 6.3.1 Solvents .4 6.3.2 Exposureconcentrations .5 6.3.3 Controls. .6 6.4 Procedure .7 6.4.1 Treatment withtest sample 1 6.4.2 Incubation. .7 6.4.3 Data collection .7 6.5 Data and reporting.. ..8 6.5.1 Treatment of results. .8 6.5.2 Evaluationand interpretation of results 6.5.3 Criteriaforavalidtest ..8 6.5.4 Test report. .9 Invitromammalian chromosomeaberrationtest .11 7.1 General. .11 7.2 Preparations .11 7.2.1 Cells .11 7.2.2 Media and culture conditions .11 7.2.3 Preparation of cultures. .11 7.2.4 Metabolic activation .11 7.2.5 Test sample preparation .12 7.3 Test conditions. ..12 7.3.1 Solvents .12 7.3.2 Exposure concentrations .12 7.3.3 Controls. ..13 7.4 Procedure. .14 7.4.1 Treatment withtest sampleorextractand harvesttime ..14 7.4.2 Chromosome preparation .14 7.4.3 Analysis. .14 7.5 Data and reporting. .15 7.5.1 Treatment of results .15 7.5.2 Evaluationand interpretation of results ..15 7.5.3 Testreport ..15 iii icensee=Zhejiang Institute of Standardization 5956617 d withoutlicensefrom IHS