BS ISO 29941-2011 Condoms Determination of nitrosamines migrating from natural rubber latex condoms《避孕套 从天然橡胶乳胶避孕套中测定亚硝胺迁移》.pdf

1、raising standards worldwideNO COPYING WITHOUT BSI PERMISSION EXCEPT AS PERMITTED BY COPYRIGHT LAWBSI Standards PublicationBS ISO 29941:2010Condoms Determination ofnitrosamines migrating fromnatural rubber latex condomsBS ISO 29941:2010 BRITISH STANDARDNational forewordThis British Standard is the UK

2、 implementation of ISO 29941:2010.The UK participation in its preparation was entrusted to TechnicalCommittee CH/157, Mechanical contraceptives.A list of organizations represented on this committee can beobtained on request to its secretary.This publication does not purport to include all the necess

3、aryprovisions of a contract. Users are responsible for its correctapplication. BSI 2011ISBN 978 0 580 65906 5ICS 11.200Compliance with a British Standard cannot confer immunity fromlegal obligations.This British Standard was published under the authority of theStandards Policy and Strategy Committee

4、 on 31 January 2011.Amendments issued since publicationDate Text affectedBS ISO 29941:2010Reference numberISO 29941:2010(E)ISO 2010INTERNATIONAL STANDARD ISO29941First edition2010-12-15Condoms Determination of nitrosamines migrating from natural rubber latex condoms Prservatifs Dosage des nitrosamin

5、es migrant des prservatifs en latex de caoutchouc naturel BS ISO 29941:2010ISO 29941:2010(E) PDF disclaimer This PDF file may contain embedded typefaces. In accordance with Adobes licensing policy, this file may be printed or viewed but shall not be edited unless the typefaces which are embedded are

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8、ting to it is found, please inform the Central Secretariat at the address given below. COPYRIGHT PROTECTED DOCUMENT ISO 2010 All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means, electronic or mechanical, including pho

9、tocopying and microfilm, without permission in writing from either ISO at the 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 Sw

10、itzerland ii ISO 2010 All rights reservedBS ISO 29941:2010ISO 29941:2010(E) ISO 2010 All rights reserved iiiContents Page Foreword iv 1 Scope1 2 Normative references1 3 Terms and definition .1 4 Principle .1 5 Reagents and materials 2 6 Apparatus.3 7 Procedure.5 8 Calculation and evaluation of the r

11、esults of the N-nitrosamine content of the solution.7 9 Confirmation of the detected N-nitrosamines 8 10 Test report9 Bibliography10 BS ISO 29941:2010ISO 29941:2010(E) iv ISO 2010 All rights reservedForeword (ISO member bodies). The work of preparing International Standards is normally carried out t

12、hrough ISO technical committees. Each member body interested in a subject 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 colla

13、borates closely with the International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization. International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2. The main task of technical committees is to prepare International Sta

14、ndards. Draft International Standards adopted by the technical committees are circulated to the member bodies for voting. Publication as an International Standard requires approval by at least 75 % of the member bodies casting a vote. Attention is drawn to the possibility that some of the elements o

15、f this document may be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights. ISO 29941 was prepared by Technical Committee ISO/TC 157, Non-systemic contraceptives and STI barrier prophylactics. BS ISO 29941:2010INTERNATIONAL STANDARD ISO 29941

16、:2010(E) ISO 2010 All rights reserved 1Condoms Determination of nitrosamines migrating from natural rubber latex condoms 1 Scope This International Standard specifies a test method to determine the release of N-nitrosamines from condoms made from natural rubber latex. The method can also be used for

17、 other products such as probe covers, prophylactic dams, female condoms and condoms made from synthetic materials, although there was no experience of testing such products at the time of publication of this International Standard. 2 Normative references The following referenced documents are indisp

18、ensable 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 3696, Water for analytical laboratory use Specification and test methods ISO 4074, Natural

19、 rubber latex condoms Requirements and test methods ISO/IEC 17025, General requirements for the competence of testing and calibration laboratories 3 Terms and definition For the purposes of this document, the following terms and definitions apply. 3.1 condom medical device used by consumers, which i

20、s intended to cover and be retained on the penis during sexual activity, for purposes of contraception and prevention of sexually transmitted infections NOTE If a consumer could responsibly consider a device to be a condom (due to its shape, packaging, etc.), it is considered a condom for the purpos

21、e of this International Standard. 4 Principle WARNING Owing to their toxicity, N-nitrosamines can be detrimental to human health. The testing laboratories should take special care to observe the occupational health and safety standards. N-nitrosamines are extracted into water. After having been conc

22、entrated, the water is tested for its N-nitrosamine content by means of gas chromatography (GC) using a chemiluminescence detector. The test is performed in an environment that is free of volatile N-nitrosamines. The released N-nitrosamines are given in nanograms per grams (ng/g) of the sample. BS I

23、SO 29941:2010ISO 29941:2010(E) 2 ISO 2010 All rights reserved5 Reagents and materials IMPORTANT Owing to the fact that N-nitrosamines are decomposed by UV light, the exposure to sunlight or fluorescent light of the standardized solutions during the preparation should be avoided. Standardized solutio

24、ns, migrate solutions and water should be protected by means of aluminium foil and stored in the dark at temperatures below 5 C. Use only reagents of recognized analytical grade and only water conforming to ISO 3696, grade 3, unless otherwise specified. 5.1 Dichloromethane, which should be checked f

25、or the absence of N-nitrosamines. 5.2 Diatomaceous earth, from liquid-liquid extraction, with a specific surface area of 1 m2/g, a pore size of 3 000 nm to 8 500 nm and a particle size of 150 m to 650 m. Heat for 1 h at 200 C and wash with dichloromethane (5.1) after cooling. Another separating agen

26、t can be used providing it has been validated against diatomaceous earth. 5.3 n-Hexane. 5.4 Sodium hydroxide solution in water, c(NaOH) = 1 mol/l. 5.5 Nitrogen, with a volume fraction of at least 99,996 %. 5.6 Boiling chips. 5.7 Sintered glass frit for columns (6.3 and 6.4). 5.8 Acetone. 5.9 N-nitro

27、samine standardized solutions. Prepare standardized solutions with known quantities of the N-nitrosamines to be determined in n-hexane (5.3) in the concentration range of 100 ng/l to 300 ng/l. The following N-nitrosamines are of importance for condoms from elastomer or rubber. The list is, however,

28、not comprehensive: N-nitrosodimethylamine (NDMA); N-nitrosodiethylamine (NDEA); N-nitrosodibutylamine (NDBA). If there are indications of the presence of other N-nitrosamines relevant for toxicology or if the nature of the used vulcanization accelerators supports this indication these other N-nitros

29、amines should also be tested, examples could be: N-nitrosodibenzylamine (NDBzA); N-nitrosodiisononylamine (NDiNA), i.e. N-nitroso-3,3,5-trimethylhexylamine. 5.10 Solution of the internal standard of 200 ng/ml N-nitrosodiisopropylamin (NDiPA) in acetone (5.8). The solution shall be free of other N-ni

30、trosamines. BS ISO 29941:2010ISO 29941:2010(E) ISO 2010 All rights reserved 35.11 Water-free sodium sulfate, granulated, or a suitable phase separation filter for the Whatman apparatus. Pre-wash 30 g of sodium sulfate with 25 ml of dichloromethane (5.1). 5.12 Ammonia solution in water, c(NH3) = 0,1

31、mol/l. 5.13 Sea sand, washed with acid and calcined. 6 Apparatus Usual laboratory apparatus and, in particular, the following: 6.1 Glass vessels washed with acidic cleansing agents, shall be treated with ammonia solution (5.12), rinsed with water and dried before being used. 6.2 Drying cabinet, adju

32、stable to (40 2) C. 6.3 Glass column, with outlet and plug made from polytetrafluorethylene (PTFE). Length of the column: (300 10) mm, inner diameter: (26 1) mm. 6.4 Glass column, with outlet and plug made from polytetrafluorethylene (PTFE). Length of the column: (300 10) mm, inner diameter: (15 1)

33、mm. 6.5 Kuderna-Danish vaporizer, modified with a graduated collecting vessel and an air cooler. An alternative apparatus may be used provided that its performance has been validated against the Kuderna-Danish vaporizer. 6.6 Water bath, temperatures adjustable from 40 C to 60 C. 6.7 Vials, closable

34、with vial mouth rings and N-nitrosamine free or PTFE coated septa. 6.8 Pliers, for closing the vials (6.7). 6.9 Fibreglass plug, washed with dichloromethane (5.1). 6.10 200 ml separating funnel. 6.11 100 ml separating funnel. 6.12 Chemiluminescence detector, of sufficient sensitivity Thermal Energy

35、Analyzer, TEA1). Another analysis detector may be used providing it has been validated against the TEA. 6.13 Chromatography system. The decision regarding the selection of the chromatography system may be made by the tester. The test laboratory shall, however, provide evidence that the conditions we

36、re optimized in such a way as to achieve a sufficient separation of peaks, with the following points being observed: The system shall separate the N-nitrosamines (5.9) mentioned in this International Standard such that their peak areas can be compared with the peak area of the internal standard solu

37、tion (5.10). The system separates N-nitrodimethylamine and N-nitrodiethylamine from the mentioned N-nitrosamines. 1) Thermal Energy Analyzer is an example of a suitable product available commercially. This information is given for the convenience of the users of this International Standard and does

38、not constitute an endorsement by ISO of this product. BS ISO 29941:2010ISO 29941:2010(E) 4 ISO 2010 All rights reservedIt is possible that two separating columns are necessary to separate all the N-nitrosamines and to achieve a sufficient sensitivity for NDBzA, if it is part of the test. The followi

39、ng conditions have been found to be suitable for the determination of volatile N-nitrosamines when using gas chromatography. EXAMPLE 1 Packed columns Injector temperature: 200 C Oven temperature: 200 C Columns: 2,5 m to 3,0 m glass, outer diameter 1/8“, packed with: 15 % Carbowax 20 M, TPA on Chromo

40、sorb WHP 100/120 mesh2); or 10 % Carbowax 20 M, 2 % KOH on Chromosorb WHP 100/120 mesh; or 4,0 m to 5,0 m glass, outer diameter 1/8“, packed with: 15 % SP 1220, 1 % H3PO4on Chromosorb WAW 100/120 mesh. Temperature of the pyrolysis oven: 480 C Carrier gas: Argon, helium, or nitrogen with a flow rate

41、of (20 1) ml/min Coupling: Directly between gas chromatography column and pyrolysis oven or by applying a coupling heated to 250 C. As regards the determination of alkylphenyl-N-nitrosamines, the following conditions have been found to be suitable: Injector temperature: 150 C. Oven temperature: betw

42、een 120 C and 130 C. Columns: 2 m glass, outer diameter 1/4“, inner diameter 2,0 mm, packed with: 10 % OV-101 on Chromosorb WHP 80/100 mesh; or 3 % OV-225 on Chromosorb WHP 80/100 mesh. Temperature of the pyrolysis oven: 480 C Temperature of the coupling: 250 C. EXAMPLE 2 Capillary columns Either In

43、jector temperature: 200 C Oven temperature: 60 C, 230 C (10 C/min) Column: 25,0 m quartz capillary 0,53 mm FFAP 1 m 2) Carbowax and Chromosorb are examples of suitable products available commercially. This information is given for the convenience of the users of this International Standard and does

44、not constitute an endorsement by ISO of these products. BS ISO 29941:2010ISO 29941:2010(E) ISO 2010 All rights reserved 5Temperature of the pyrolysis oven: 480 C Temperature of the coupling: 250 C or Injector temperature: 50 C, 1 min 200 C (75 C/min) Oven temperature 40 C, 7 min 60 C (1 C/min), 230

45、C (14 C/min) Column: 30,0 m quartz capillary, 0,53 mm, SE-54-film of 2 m Temperature of the pyrolysis oven: 480 C Temperature of the coupling: 250 C. 7 Procedure 7.1 Migration of the condom material 7.1.1 For this test, use only condoms that have been tested according to ISO 4074 and conform to that

46、 standard. Use the average results of the tests for length and width for the calculations (see Clause 8). Determine the masses of three condoms. The average mass of these three reference condoms is the basis for the quantity of intact condoms to be used in the test. Cut each condom in half. Weigh (5

47、 1) g of the prepared condoms to the nearest 0,05 g and transfer them to a 50 ml Erlenmeyer flask. Add 40,0 ml of water by means of a pipette. Close the flask by means of a glass stopper, shake it cautiously so that the solution covers the prepared condoms. Store the flask in the drying cabinet (6.2

48、) for 10 min ( 30 s) at (40 2) C. Adapt the reagent quantities and the apparatus sizes proportionally if the mass of the condom material exceeds 5 g. The quantity of added internal standard solution (5.10), however, is always 1,0 ml. 7.1.2 Decant the solution from the flask to a 50 ml measuring cyli

49、nder with glass stopper, wash the condom material with 4,0 ml of water, add it to the test solution, fill with water up to the mark and mix it for at least 1 min. 7.2 Isolation of the N-nitrosamines in the solution 7.2.1 General Add 1,0 ml of the internal standard solution (5.10) and 1,0 ml of sodium hydroxide solution (5.4) to the solution in the measuring cylinder (7.1.2) by means of a pipette. The test solution can be processed according to procedure A o