1、April 2011 Translation by DIN-Sprachendienst.English price group 13No 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!$n(“1759405www.din.deDDIN EN ISO 10808Nanotechnologies Characterization of nanoparticles in inhalation exposure chambers forinhalation toxicity testing (ISO 10808:2010)English translation of DIN EN ISO 10808:2011-04Nanotechnologien Charakterisierung von Nanopartikeln in Inhalationskammern zur
3、 Prfung auf Toxizittnach Inhalation (ISO 10808:2010)Englische bersetzung von DIN EN ISO 10808:2011-04Nanotechnologies Caractrisation des nanoparticules dans les chambres dinhalation par exposition pour lesessais de toxicit par inhalation (ISO 10808:2010)Traduction anglaise de DIN EN ISO 10808:2011-0
4、4www.beuth.deDocument comprises pagesIn case of doubt, the German-language original shall be considered authoritative.2403.11 DIN EN ISO 10808:2011-04 A comma is used as the decimal marker. National foreword This standard has been prepared by Technical Committee ISO/TC 229 “Nanotechnologies” in coll
5、aboration 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 Testing Standards Committee), Working Committees NA 06
6、2-08-17 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 9276-6 DIN ISO 9276-6 ISO 10801 DIN EN ISO 10801 ISO/IEC 17025 DIN EN ISO/IEC 17025 ISO/TS 27687 DIN SPEC
7、 1121 National Annex NA (informative) Bibliography DIN EN ISO 10801, Nanotechnologies Generation of metal nanoparticles with the evaporation/ condensation method for inhalation toxicity testing DIN EN ISO/IEC 17025, General requirements for the competence of testing and calibration laboratories DIN
8、ISO 9276-6, Representation of results of particle size analysis Part 6: Descriptive and quantitative representation of particle shape and morphology DIN SPEC 1121, Nanotechnologies Terminology and definitions for nano-objects Nanoparticle, nanofibre and nanoplate 2 EUROPEAN STANDARD NORME EUROPENNE
9、EUROPISCHE NORM EN ISO 10808 December 2010 ICS 07.030 English Version Nanotechnologies Characterization of nanoparticles in inhalation exposure chambers for inhalation toxicity testing (ISO 10808:2010) Nanotechnologies Caractrisation des nanoparticules dans les chambres dinhalation par exposition po
10、ur les essais de toxicit par inhalation (ISO 10808:2010) Nanotechnologien Charakterisierung von Nanopartikeln in Inhalationskammern zur Prfung auf Toxizitt nach Inhalation (ISO 10808:2010) This European Standard was approved by CEN on 10 December 2010. CEN members are bound to comply with the CEN/CE
11、NELEC 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 the CEN-CENELEC Management Centre
12、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 Centre has the same status as the of
13、ficial 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, Norway, Poland, Portugal, Romania, Sl
14、ovakia, 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 and by any means reserved worldwi
15、de for CEN national Members. Ref. No. EN ISO 10808:2010: EContents Page Foreword .3 Introduction.4 1 Scope5 2 Normative references5 3 Terms and definitions .5 3.1 Particle measuring systems.6 4 Test substance monitoring method 8 4.1 Principle .8 4.1.1 Exposure 8 4.1.2 Particle properties.8 4.2 Prepa
16、ration of system.8 4.3 Study.9 5 Specific monitoring method.9 5.1 Requirements for number-based particle size distribution and mass concentration .9 5.2 Measurement of number-based particle size distribution 9 5.3 Mass concentration measurement 10 5.4 Inhalation exposure chamber 10 6 Assessment of r
17、esults 11 7 Test report11 Annex A (informative) Example of nanoparticle characterization for inhalation toxicity testing.13 Bibliography21 EN ISO 10808:2010 (E) DIN EN ISO 10808:2011-04 2Foreword This document (EN ISO 10808:2010) has been prepared by Technical Committee ISO/TC 229 “Nanotechnologies”
18、 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 identical text or by endorsement, at the latest by June 2011, and conflicting nationa
19、l 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 responsible for identifying any or all such patent rights. According to the CEN/CENELE
20、C 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, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
21、 Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and the United Kingdom. Endorsement notice The text of ISO 10808:2010 has been approved by CEN as a EN ISO 10808:2010 without any modification. EN ISO 10808:2010 (E) DIN EN ISO 10808:20
22、11-04 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 to nanoparticles continues to increase as the applications expand. In particular
23、, workers in nanotechnology-based industries are at risk of being exposed to nanoparticles. If nanoparticles are liberated from products, the public could be exposed as well. Although toxicity screening using instillation of nanomaterials provides important information, it does not reflect the actua
24、l scenario of inhalation exposure and does not provide the data required for inhalation exposure risk assessment. In addition, while inhalation toxicology using rats is the norm at this time, it is desirable to replace this antiquated method with a human-relevant assay10. The inhalation toxicity of
25、nanoparticles is of particular concern in ensuring the health of workers and consumers. In order to conduct inhalation toxicity studies of nano-sized particles, the monitoring of concentration, size and distribution of nano-sized particles in the inhalation chamber is necessary. The conventional met
26、hods of fine or coarse particle monitoring, such as weight-based mass dose monitoring, are considered insufficient for nanoparticles, since nano-specific parameters (particle surface area, particle number, etc.) might be critical determinants, and if so, should also be monitored. This International
27、Standard proposes a battery of inhalation toxicity testing chamber monitoring, including a differential mobility analyzing system (DMAS), for measuring particle number, size, distribution, surface area and estimated mass dose, as well as morphological examination using transmission electron microsco
28、py (TEM) or scanning electron microscopy (SEM) equipped with an energy dispersive X-ray analyzer (TEM-EDXA) for chemical composition. This International Standard also includes conventional mass dose monitoring and other physicochemical monitoring, for use when deemed a necessary parameter for toxici
29、ty determination. This method evaluates nano-sized particle surface area, mass dose, particle distribution, composition and dispersion to support effective analysis of inhalation toxicity testing results 131718. EN ISO 10808:2010 (E) DIN EN ISO 10808:2011-04 41 Scope This International Standard spec
30、ifies requirements for, and gives guidance on, the characterization of airborne nanoparticles in inhalation exposure chambers for the purpose of inhalation toxicity studies in terms of particle mass, size distribution, number concentration and composition. 2 Normative references The following refere
31、nced 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 referenced document (including any amendments) applies. ISO 10312, Ambient air Determination of asbestos fibres Direct transf
32、er transmission electron microscopy method ISO 15900, Determination of particle size distribution Differential electrical mobility analysis for aerosol particles ISO/TS 27687, Nanotechnologies Terminology and definitions for nano-objects Nanoparticle, nanofibre and nanoplate OECD Test Guideline 403
33、(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)OECD Guidance Document 39 (GD 39), Acute Inhalation Toxicity Testing1)3 Terms and definitions For the pur
34、poses of this document, the terms and definitions given in ISO 15900 and ISO/TS 27687 and the following apply. 1) Organization for Economic Cooperation and Development (OECD) publication. EN ISO 10808:2010 (E) DIN EN ISO 10808:2011-04 53.1 Particle measuring systems 3.1.1 differential electrical mob
35、ility 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 electrical force on each part
36、icle 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 Adapted from ISO 15900:2009, d
37、efinition 2.7. 3.1.2 differential mobility analyzing system DMAS system used to measure the size distribution of submicrometre aerosol particles consisting of a DEMC, a particle charge conditioner, flow meters, a particle detector, interconnecting plumbing, a computer and suitable software NOTE Adap
38、ted from ISO 15900:2009, definition 2.8. 3.1.3 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 hund
39、red 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 Adapted from ISO 15900:2009, definition 2.5. 3.2 inhalation exposure chamber inhalatio
40、n 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 403, 412, 413
41、. 3.3 nanoparticle generation system device used to make nanoparticle aerosol with controlled size distribution and concentration 3.4 breathing zone location from which the experimental animal breathes NOTE 1 For an unrestrained, non-caged animal, this will be the entire volume of the inhalation cha
42、mber. For a restrained or caged animal, this will be the range of motion for the animals nose. For a masked animal, this will be the small volume in front of the nostrils. EN ISO 10808:2010 (E) DIN EN ISO 10808:2011-04 6NOTE 2 The term “breathing zone” is used to ensure test atmosphere samples are o
43、btained from the same location as that in which the animal breathes. An undesirable sampling approach would be one where concentration measurements are obtained at the top of the inhalation chamber while the animal is exposed at the bottom. 3.5 geometric mean diameter GMD measure of central tendency
44、 of particle size distribution using the logarithm of particle diameters, computed for the DMAS by ()lnln(GMD)niiimNdN=where diis the midpoint diameter for the size channel, i; N is the total concentration; Niis the concentration within the size channel, i; m is the first channel; n is the last chan
45、nel. NOTE The GMD is normally computed from particle counts and when noted may be based on surface area or particle volume with appropriate weighting. 3.6 geometric standard deviation GSD measure of width or spread of particle sizes, computed for the DMAS by ()2ln ln GMDln(GSD)1niiimNdN=3.7 count me
46、dian 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) o
47、f 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; EN ISO 10808:2010 (E) DIN EN ISO 10808:2011-04 7r is the dimensionality (type of quantity) of a distribution, where r = 0 is the number, r = 1 is the length, r = 2 is the area, and r
48、 = 3 is the volume or mass; s is the standard deviation of the density distribution; x50,ris the median particle size of a cumulative distribution of dimensionality, r. 4 Test substance monitoring method 4.1 Principle 4.1.1 Exposure Precise characterization of the test substance exposure is essential for an inhalation toxicology study. The objective in nanoparticle inhalation toxicology is to establish a quantitative relationship between the observed toxicological outcome and the dose metrics used in
