1、April 2011 Translation by DIN-Sprachendienst.English price group 14No part of this translation may be reproduced without prior permission ofDIN Deutsches Institut fr Normung e. V., Berlin. Beuth Verlag GmbH, 10772 Berlin, Germany,has the exclusive right of sale for German Standards (DIN-Normen).ICS
2、07.030!$nb0“1756313www.din.deDDIN EN ISO 10801Nanotechnologies Generation of metal nanoparticles for inhalation toxicity testing usingthe evaporation/condensation method (ISO 10801:2010)English translation of DIN EN ISO 10801:2011-04Nanotechnologien Erzeugung von Metall-Nanopartikeln zur Prfung auf
3、Toxizitt nach Inhalation unterVerwendung des Verdampfungs-/Kondensationsverfahrens (ISO 10801:2010)Englische bersetzung von DIN EN ISO 10801:2011-04Nanotechnologies Gnration de nanoparticules de mtal pour essais de toxicit par inhalation en utilisant lamthode de condensation/vaporation (ISO 10801:20
4、10)Traduction anglaise de DIN EN ISO 10801:2011-04www.beuth.deDocument comprises pagesIn case of doubt, the German-language original shall be considered authoritative.2803.11 DIN EN ISO 10801:2011-04 A comma is used as the decimal marker. National foreword This standard has been prepared by Technica
5、l Committee ISO/TC 229 “Nanotechnologies” in collaboration with Technical Committee CEN/TC 352 “Nanotechnologies”. BSI, United Kingdom, holds the secretariats of both Technical Committees. The responsible German body involved in its preparation was the Normenausschuss Materialprfung (Materials Testi
6、ng Standards Committee), Working Committees NA 062-08-17 AA Nanotechnologien and NA 062-08-17-03 UA Gesundheits- und Umweltaspekte. The DIN Standards corresponding to the International Standards referred to in this document are as follows: ISO 9276-1 DIN ISO 9276-1 ISO 10808 DIN EN ISO 10808 ISO/TS
7、27687 DIN SPEC 1121 ISO/IEC 17025 DIN EN ISO/IEC 17025 National Annex NA (informative) Bibliography DIN EN ISO 10808, Nanotechnologies Characterization of nanoparticles in inhalation exposure chambers for inhalation toxicity testing DIN EN ISO/IEC 17025, General requirements for the competence of te
8、sting and calibration laboratories DIN ISO 9276-1, Representation of results of particle size analysis Part 1: Graphical representation DIN SPEC 1121, Nanotechnologies Terminology and definitions for nano-objects Nanoparticle, nanofibre and nanoplate 2 EUROPEAN STANDARD NORME EUROPENNE EUROPISCHE NO
9、RM EN ISO 10801 December 2010 ICS 07.030 English Version Nanotechnologies Generation of metal nanoparticles for inhalation toxicity testing using the evaporation/condensation method (ISO 10801:2010) Nanotechnologies Gnration de nanoparticules de mtal pour essais de toxicit par inhalation en utilisan
10、t la mthode de condensation/vaporation (ISO 10801:2010) Nanotechnologien Erzeugung von Metall-Nanopartikeln zur Prfung auf Toxizitt nach Inhalation unter Verwendung des Verdampfungs-/Kondensationsverfahrens (ISO 10801:2010) This European Standard was approved by CEN on 14 December 2010. CEN members
11、are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this EuropeanStandard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such national standards may be obtained on application to
12、 the CEN-CENELEC Management Centre or to any CEN member. This European Standard exists in three official versions (English, French, German). A version in any other language made by translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management C
13、entre has the samestatus as the official versions. CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Nor
14、way, Poland,Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom. EUROPEAN COMMITTEE FOR STANDARDIZATION COMIT EUROPEN DE NORMALISATION EUROPISCHES KOMITEE FR NORMUNG Management Centre: Avenue Marnix 17, B-1000 Brussels 2010 CEN All rights of exploitation in any form
15、and by any means reserved worldwide for CEN national Members. Ref. No. EN ISO 10801:2010: EContents PageForeword .3 Introduction.4 1 Scope5 2 Normative references5 3 Terms and definitions .5 4 Principle .7 4.1 Generation7 4.2 Preparation of system.8 5 Requirements.8 5.1 Capacity and control.8 5.2 Na
16、noparticle properties 9 5.3 Exposure chamber atmosphere.9 5.4 System operational safety9 6 Characterization of generator performance .10 6.1 Requirements for particle size distribution and mass concentration .10 6.2 Particle size distribution measurement 10 6.2.1 Sampling with DMAS.10 6.2.2 Sampling
17、 for microscopy .10 6.3 Mass concentration measured by filter sampling10 6.3.1 Filter sampling for aerosol mass concentration 11 6.3.2 Frequency of sampling .11 7 Nanoparticle generation specifications 11 7.1 Test particle purity/impurities 117.2 Size range.11 7.3 Number concentration 11 7.4 Nanopar
18、ticle shape .11 7.5 Stability.11 7.6 Animal exposure12 8 Assessment of results 12 9 Test report12 Annex A (informative) Example method for evaporation/condensation generation of silver nanoparticles .13 Bibliography25 EN ISO 10801:2010 (E) DIN EN ISO 10801:2011-04 2Foreword This document (EN ISO 108
19、01:2010) has been prepared by Technical Committee ISO/TC 229 “Nanotechnologies” in collaboration with Technical Committee CEN/TC 352 “Nanotechnologies” the secretariat of which is held by BSI. This European Standard shall be given the status of a national standard, either by publication of an identi
20、cal text or by endorsement, at the latest by June 2011, and conflicting national standards shall be withdrawn at the latest by June 2011. Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. CEN and/or CENELEC shall not be held respons
21、ible for identifying any or all such patent rights. According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland
22、, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and the United Kingdom. Endorsement notice The text of ISO 10801:2010 has been approved by CEN as a EN ISO
23、 10801:2010 without any modification. EN ISO 10801:2010 (E) DIN EN ISO 10801:2011-04 3Introduction The number of nanotechnology-based consumer products containing silver, gold, carbon, zinc oxide, titanium dioxide and silica nanoparticles is growing very rapidly. The population at risk of exposure t
24、o nanoparticles continues to increase as the applications expand. In particular, workers in nanotechnology-based industries are at risk of being exposed to manufactured nanoparticles. If nanoparticles are liberated from products, the public could be exposed as well. There is currently limited, but g
25、rowing, knowledge about the toxicity of nano-sized particles. The processes of nanoparticle production include gas-phase, vapour-phase, colloidal and attrition processes. Potential paths of exposure include inhalation, dermal and ingestion. Inhalation may arise from direct leakage from gas-phase and
26、 vapour-phase processes, airborne contamination of the workplace from deposition or product recovery and handling of product, or post-recovery processing and packing7. Exposure to manufactured nano-sized particles might occur during production, use and disposal in the ambient air or workplace and is
27、 of concern for public and occupational health. There are currently neither generally accepted methods of inhalation toxicology testing for nano-sized particles nor specific nanoparticle generation methods for such testing. The ability to disperse respirable nano-sized particles from powders has bee
28、n an obstacle to evaluating the effects of inhalation of nano-sized particles on the respiratory system. Although it is possible to disperse nanoparticles in air from powders, the size of the particles so generated may be larger than desired due to aggregation and agglomeration. In order to gain vit
29、al information for evaluating the health effects of nanoparticles by inhalation, nano-sized particles need to be generated and transported to a test environment containing experimental animals for testing short- or long-term inhalation toxicity. The nanoparticle generation method based on evaporatio
30、n of metal (silver in this example) and subsequent condensation is capable of providing a consistent particle size distribution and stable number concentrations, suitable for short- or long-term inhalation toxicity study. This International Standard provides a method for stable silver nanoparticle g
31、eneration with particle sizes up to 100 nm. A detailed method is described in Annex A. The generation method provided here has sufficient stability for continuous inhalation toxicity testing up to 90 days. The generated nanoparticles can be used in various experimental systems, including high-throug
32、hput human cell-based labs-on-a-chip, a variety of additional in-vitro methods 891011, as well as the animal experiments that may still be performed at this time, which include, but are not limited to, whole-body, head-only and nose-only. The method is not limited to the silver nanoparticles used in
33、 this example and may be used to generate other metallic nanoparticles with a similar melting temperature and evaporation rate, such as gold. However, this method is not applicable to the generation of nanoparticles of all metals. EN ISO 10801:2010 (E) DIN EN ISO 10801:2011-04 41 Scope This Internat
34、ional Standard gives requirements and recommendations for generating metal nanoparticles as aerosols suitable for inhalation toxicity testing by the evaporation/condensation method. Its application is limited to metals such as gold and silver which have been proven to generate nanoparticles suitable
35、 for inhalation toxicity testing using the technique it specifies (see Annex A). 2 Normative references The following referenced documents are indispensable for the application of this document. For dated references, only the edition cited applies. For undated references, the latest edition of the r
36、eferenced document (including any amendments) applies. ISO/TS 27687, Nanotechnologies Terminology and definitions for nano-objects Nanoparticle, nanofibre and nanoplate ISO 15900, Determination of particle size distribution Differential electrical mobility analysis for aerosol particles ISO/IEC 1702
37、5, General requirements for the competence of testing and calibration laboratories OECD Test Guideline (TG) 403, Acute Inhalation Toxicity1)OECD Test Guideline 412 (TG) 412, Subacute Inhalation Toxicity: 28-Day Study1)OECD Test Guideline 413 (TG) 413, Subchronic Inhalation Toxicity: 90-day Study1)3
38、Terms and definitions For the purposes of this document, the terms and definitions given in ISO/TS 27687 and ISO 15900 and the following apply. 3.1 differential mobility analysing system DMAS system used to measure the size distribution of submicrometre aerosol particles consisting of a DEMC, a part
39、icle charge conditioner, flow meters, a particle detector, interconnecting plumbing, a computer and suitable software NOTE Adapted from ISO 15900:2009, definition 2.8. 1) Organization for Economic Cooperation and Development (OECD) publication. EN ISO 10801:2010 (E) DIN EN ISO 10801:2011-04 53.2 dif
40、ferential electrical mobility classifier DEMC differential electrical mobility spectrometer DEMS classifier that is able to select aerosol particle sizes from a distribution that enters it and pass only selected sizes to the exit NOTE 1 A DEMC classifies aerosol particle sizes by balancing the elect
41、rical force on each particle in an electrical field with its aerodynamic drag force. Classified particles have different sizes due to their number of electrical charges and a narrow range of electrical mobility determined by the operating conditions and physical dimensions of the DEMC. NOTE 2 Adapte
42、d from ISO 15900:2009, definition 2.7. 3.3 condensation particle counter CPC instrument that detects particles and that can be used to calculate particle number concentration given the known flow rates into the detector NOTE 1 The range of particles detected are usually smaller than several hundred
43、nanometers and larger than a few nanometers. A CPC is one possible detector for use with a DEMC. NOTE 2 In some cases, a condensation particle counter may be called a condensation nucleus counter (CNC). NOTE 3 This definition is different from the one given in ISO 15900. 3.4 inhalation exposure cham
44、ber inhalation chamber exposure chamber system prepared to expose experimental animals to an inhaled test substance of predetermined duration and dose by either the nose-only or whole-body method NOTE 1 The term “nose-only” is synonymous with “head-only” or “snout-only”. NOTE 2 Adapted from OECD TG
45、403, OECD TG 412, OECD TG 413. 3.5 evaporation/condensation nanoparticle generator system device used to make a nanoparticle aerosol by the evaporation/condensation method, which can be connected to an inhalation chamber or other toxicity testing device 3.6 geometric mean diameter GMD measure of the
46、 central tendency of particle size distribution using the logarithm of particle diameters, computed for the DMAS by ()lnln(GMD)niiimNdN=where diis the midpoint diameter for size channel i; N is the total concentration; Niis the concentration within size channel i; EN ISO 10801:2010 (E) DIN EN ISO 10
47、801:2011-04 6m is the first channel; n is the last channel. NOTE The GMD is normally computed from particle counts and, when noted, may be based on surface area or particle volume with appropriate weighting. 3.7 geometric standard deviation GSD measure of width or spread of particle sizes, computed
48、for the DMAS by ()2ln ln GMDln(GSD)1niiimNdN=3.8 count median diameter CMD diameter equal to GMD for particle counts assuming a logarithmic normal distribution NOTE The general form of the relationship as described in ISO 9276-5 is ()250, 50,CMD erpsrpxx= where e is the base of natural logarithms, e = 2,718 28; p is the dimensionality (type of quantity) of a distribution, where p = 0 is the number, p = 1 is the length, p = 2 is the area, and p = 3 is the volume or mass; r is the dimensionality (typ
