1、BSI Standards Publication PD ISO/TR 16197:2014 Nanotechnologies Compilation and description of toxicological screening methods for manufactured nanomaterialsPD ISO/TR 16197:2014 PUBLISHED DOCUMENT National foreword This Published Document is the UK implementation of ISO/TR 16197:2014. The UK partici
2、pation in its preparation was entrusted to Technical Committee NTI/1, Nanotechnologies. A list of organizations represented on this committee can be obtained on request to its secretary. This publication does not purport to include all the necessary provisions of a contract. Users are responsible fo
3、r its correct application. The British Standards Institution 2014. Published by BSI Standards Limited 2014 ISBN 978 0 580 74485 3 ICS 07.030 Compliance with a British Standard cannot confer immunity from legal obligations. This Published Document was published under the authority of the Standards Po
4、licy and Strategy Committee on 31 May 2014. Amendments/corrigenda issued since publication Date T e x t a f f e c t e dPD ISO/TR 16197:2014 ISO 2014 Nanotechnologies Compilation and description of toxicological screening methods for manufactured nanomaterials Nanotechnologies Compilation et descript
5、ion des mthodes de criblage toxicologiques pour les nanomatriaux manufacturs TECHNICAL REPORT ISO/TR 16197 First edition 2014-05-15 Reference number ISO/TR 16197:2014(E)PD ISO/TR 16197:2014ISO/TR 16197:2014(E)ii ISO 2014 All rights reserved COPYRIGHT PROTECTED DOCUMENT ISO 2014 All rights reserved.
6、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 t
7、he address below or ISOs member body in the country of the requester. ISO copyright office Case postale 56 CH-1211 Geneva 20 Tel. + 41 22 749 01 11 Fax + 41 22 749 09 47 E-mail copyrightiso.org Web www.iso.org Published in SwitzerlandPD ISO/TR 16197:2014ISO/TR 16197:2014(E) ISO 2014 All rights reser
8、ved iii Contents Page Foreword iv Introduction v 1 Scope . 1 2 Normative references 1 3 T erms and definitions . 1 4 Symbols (and abbreviated terms) 3 5 Background 3 5.1 Role and relevance of toxicological screening for the safety evaluation of manufactured NMs 3 5.2 Toxicological screening as part
9、of tiered approaches to toxicological assessment of manufactured NMs 4 5.3 Discussion of relevant dosing for toxicological screening . 5 5.4 Discussion of the relationship between this Technical Report and ISO/DTR 16196, Compilation and description of sample preparation and dosing methods for manufa
10、ctured NMs 6 5.5 Discussion of the relationship between this Technical Report and ISO/TR 13014, Nanotechnologies Guidance on physico-chemical characterization of engineered nanoscale materials for toxicological assessment 6 5.6 Review of other relevant international activities and published document
11、s . 6 6 Methods for toxicological screening related to human health . 7 6.1 General . 7 6.2 Positive and negative controls for nanomaterial toxicity testing 7 6.3 Relevant methods for in vitro toxicological screening of manufactured NMs 8 6.4 Relevant methods for in vivo toxicological screening of m
12、anufactured NMs .19 7 Methods for toxicological screening related to the environment 20 7.1 Introduction .20 7.2 Environmental fate and distribution 20 7.3 Environmental degradation and transformation .21 7.4 Environmental biopersistence and bioaccumulation . 21 Bibliography .22PD ISO/TR 16197:2014I
13、SO/TR 16197:2014(E) Foreword ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies (ISO member bodies). The work of preparing International Standards is normally carried out through ISO technical committees. Each member body interested in a s
14、ubject for which a technical committee has been established has the right to be represented on that committee. International organizations, governmental and non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the International Electrotechnical Commission
15、(IEC) on all matters of electrotechnical standardization. The procedures used to develop this document and those intended for its further maintenance are described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the different types of ISO documents should
16、be noted. This document was drafted in accordance with the editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives). Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. ISO shall not be held responsible for ident
17、ifying any or all such patent rights. Details of any patent rights identified during the development of the document will be in the Introduction and/or on the ISO list of patent declarations received (see www.iso.org/patents). Any trade name used in this document is information given for the conveni
18、ence of users and does not constitute an endorsement. For an explanation on the meaning of ISO specific terms and expressions related to conformity assessment, as well as information about ISOs adherence to the WTO principles in the Technical Barriers to Trade (TBT) see the following URL: Foreword -
19、 Supplementary information The committee responsible for this document is ISO/TC 229, Nanotechnologies.iv ISO 2014 All rights reservedPD ISO/TR 16197:2014ISO/TR 16197:2014(E) Introduction This Technical Report provides a compilation of methods intended to aid the process of toxicological screening o
20、f engineered and manufactured nanomaterials prior to full-scale toxicological testing, analysis, and risk assessment. Toxicological screening methods focus on providing information and tools that can be used in decision-making processes. For instance, this Technical Report provides information on me
21、thods that can be used to screen nanomaterials in order to determine whether to continue development of a nanomaterial itself and/or a product containing a nanomaterial; determine whether to take on the cost of performing the remaining tiers within a complete tiered-testing strategy; or determine wh
22、ether appropriate controls are in place to continue nanomaterial research in the laboratory. This Technical Report is not intended to supplant or compete with any existing regulatory requirements regarding nanomaterial testing, use, and disposal, nor does it provide a list of validated tests for thi
23、s purpose. The information provided is consistent with other International Standards. For example, its sister document Compilation and Description of Sample Preparation and Dosing Methods for Manufactured NMs is developed in concert and discusses methods used to prepare samples in various relevant m
24、edia for toxicological studies. ISO 10993-18 1specifically addresses the evaluation of the chemical characterization of materials used in medical devices, ISO 14971 2points out that a toxicological risk analysis should take into account the chemical nature of the materials, and ISO/TR 13014 3address
25、es issues pertaining to the materials themselves. ISO/TR 13121 4describes a process for identifying, evaluating, and communicating the potential risks of manufactured nanomaterials and provides guidance on tiered nanomaterial toxicity testing. ISO 2014 All rights reserved vPD ISO/TR 16197:2014PD ISO
26、/TR 16197:2014Nanotechnologies Compilation and description of toxicological screening methods for manufactured nanomaterials 1 Scope This Technical Report provides a compilation and description of in vitro and in vivo methods that can be useful for the toxicological, including ecotoxicological scree
27、ning of engineered and manufactured nanomaterials. Toxicological screening tests included in this Technical Report can be used for such purposes as early decision-making in research and product development, rapid feedback on potential toxicological/safety concerns, or for the preliminary assessment
28、of manufactured nanomaterials. This Technical Report is divided between screening assays related to humans and screening assays related to the environment. A screening test is a relatively simple, inexpensive test that can be administered easily and provides an indication of potential adverse outcom
29、es and effects on human health or the environment. The Technical Report is intended to complement other international efforts that address nanomaterial toxicology by focusing on screening methods suited for preliminary assessment and is not intended to duplicate similar efforts in other internationa
30、l organizations such as the Organization for Economic Cooperation and Development (OECD). If screening provides an early indication of hazard, the guidance will refer to other organizations approaches for full-scale toxicological assessment or further tiered studies. 2 Normative references The follo
31、wing documents, in whole or in part, are normatively referenced in this document and are indispensable for its application. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies. ISO/TS 27687:200
32、8, Nanotechnologies Terminology and definitions for nano-objects Nanoparticle, nanofibre and nanoplate ISO/TS 80004-1, Nanotechnologies Vocabulary Part 1: Core terms 3 T erms a nd definiti ons For the purposes of this document, the terms and definitions given in ISO/TS 27687:2008 and ISO/TS 80004-1
33、and the following apply. 3.1 agglomerate collection of weakly bound particles or aggregates or mixtures of the two where the resulting external surface area is similar to the sum of the surface areas of the individual components Note 1 to entry: The forces holding an agglomerate together are weak fo
34、rces, for example van der Waals forces, or simple physical entanglement. Note 2 to entry: Agglomerates are also termed secondary particles and the original source particles are termed primary particles. SOURCE: ISO/TS 27867:2008, 3.2 TECHNICAL REPORT ISO/TR 16197:2014(E) ISO 2014 All rights reserved
35、 1PD ISO/TR 16197:2014ISO/TR 16197:2014(E) 3.2 aggregate particle comprising strongly bonded or fused particles where the resulting external surface area can be significantly smaller than the sum of calculated surface areas of the individual components Note 1 to entry: The forces holding an aggregat
36、e together are strong forces, for example covalent bods, or those resulting from sintering or complex physical entanglement. Note 2 to entry: Aggregates are also termed secondary particles and the original source particles are termed primary particles. SOURCE: ISO/TS 27867:2008, 3.3 3.3 manufactured
37、 nanomaterial nanomaterial intentionally produced for commercial purposes to have specific properties or specific composition SOURCE: ISO/TS 80004-1, 2.9 3.4 n a no f ibr e nano-object with two external dimensions in the nanoscale and the third dimension significantly larger Note 1 to entry: A nanof
38、ibre can be flexible or rigid. Note 2 to entry: The two similar external dimensions are considered to differ in size by less than three times and the significantly larger external dimension is considered to differ from the other two by more than three times. Note 3 to entry: The largest external dim
39、ension is not necessarily in the nanoscale. SOURCE: ISO/TS 27687:2008, 4.3 3.5 nanomaterial material with any external dimension in the nanoscale or having internal structure or surface structure in the nanoscale Note 1 to entry: This generic term is inclusive of nano-object and nanostructured mater
40、ial. Note 2 to entry: See also engineered nanomaterial, manufactured nanomaterial, and incidental nanomaterial. SOURCE: ISO/TS 80004-1, 2.4 3.6 nano-object material with one, two, or three external dimensions in the nanoscale Note 1 to entry: Generic term for all discrete nanoscale objects. SOURCE:
41、ISO/TS 27687:2008, 2.2 3.7 nanoparticle nano-object with all three external dimensions in the nanoscale Note 1 to entry: If the lengths of the longest to the shortest axes of the nano-object differ significantly (typically by more than three times), the terms nanorod or nanoplate are intended to be
42、used instead of the term nanoparticle. SOURCE: ISO/TS 27687:2008, 4.12 ISO 2014 All rights reservedPD ISO/TR 16197:2014ISO/TR 16197:2014(E) 3.8 nanoscale size range from approximately 1 nm to 100 nm Note 1 to entry: Properties that are not extrapolations from a larger size will typically, but not ex
43、clusively, be exhibited in this size range. For such properties, the size limits are considered approximate. Note 2 to entry: The lower limit in this definition (approximately 1 nm) is introduced to avoid single and small groups of atoms from being designated as nano-objects or elements of nanostruc
44、tures, which might be implied by the absence of a lower limit. SOURCE: ISO/TS 27687:2008, 2.1 3.9 nanotube hollow nanofibre SOURCE: ISO/TS 27687:2008, 4.4 3.10 particle minute piece of matter with defined physical boundaries Note 1 to entry: A physical boundary can also be described as an interface.
45、 Note 2 to entry: A particle can move as a unit. Note 3 to entry: This general particle definition applies to nano-objects. SOURCE: ISO/TS 27687:2008, 3.1 4 Symbols (and abbreviated terms) ASTM American Society for Testing and Materials ESR Electron Spin Resonance IT Intracheal ITS Integrated Testin
46、g Strategies (or in some cases, Intelligent Testing Strategies) LTE Lymphoid Tissue Equivalent Module NMs nanomaterials OECD Organization for Economic Cooperation and Development PBS phosphate buffer saline PTE peripheral tissue equivalent ROS reactive oxygen species STS standard toxicity studies 5
47、Background 5.1 Role and relevance of toxicological screening for the safety evaluation of manufac- tured NMs It is a challenge to keep up with the number of emerging NMs with novel properties and to toxicologically assay new materials prior to human exposure, including occupational and environmental
48、 exposure. ISO 2014 All rights reserved 3PD ISO/TR 16197:2014ISO/TR 16197:2014(E) Because virtually every element on the periodic table could be explored in nanotechnology, the potential diversity of NMs makes it impractical to utilize our current testing paradigms to evaluate every new nanomaterial
49、. High-throughput toxicological screening is essential to keeping pace with the rate of NMs currently emerging on the market. Such screening is typically conducted using cell culture or other in vitro techniques due to cost, infrastructure, and time constraints; such considerations prevent most whole animal studies. In addition, there is a worldwide effort to diminish the use of in vivo animal studies as presented in the 3R (replacement, reduction, refinement) principle. 5 The purpose of a screening test
