ASTM F749-2013 Standard Practice for Evaluating Material Extracts by Intracutaneous Injection in the Rabbit《用兔子皮内注射法评定材料提取物的标准实施规程》.pdf

1、Designation: F74998 (Reapproved 2012)F74913 Standard Practice for Evaluating Material Extracts by Intracutaneous Injection in the Rabbit 1 ThisstandardisissuedunderthexeddesignationF749;thenumberimmediatelyfollowingthedesignationindicatestheyearoforiginal adoptionor,inthecaseofrevision,theyearoflast

2、revision.Anumberinparenthesesindicatestheyearoflastreapproval.Asuperscript epsilon () indicates an editorial change since the last revision or reapproval. 1. Scope 1.1 This practice is a nonspecic, acute toxicity test used to help determine the biocompatibility of materials used in medical devices.

3、1.2 The liquids injected into the rabbits are those obtained by Practice F619 where the extraction vehicles are saline, vegetable oil, or other liquids simulating human body uids. 1.3 Thispracticeisoneofseveraldevelopedfortheassessmentofthebiocompatibilityofmaterials.PracticeF748mayprovide guidance

4、for the selection of appropriate methods for testing materials for a specic application. 1.4 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard. 2. Referenced Documents 2.1 ASTM Standards: 2 F619Practice for Extraction of Medical

5、 Plastics F748Practice for Selecting Generic Biological Test Methods for Materials and Devices 3. Summary of Practice 3.1 TheextractliquidispreparedinaccordancewithPracticeF619.Theextractionvehiclesaresalineandvegetableoil,orother extraction vehicles can be used, as described in Practice F619. The e

6、xtract liquid is injected into rabbits and the animals are observed at regular intervals for 72 h for erythema, edema, or necrosis. 4. Signicance and Use 4.1 This practice is to be used to help assess the biocompatibility of materials used in medical devices. It is an acute toxicological test design

7、ed to detect the presence of injurious leachable substances. 4.2 This practice may not be appropriate for all types of implant applications. The user is cautioned to consider the appropriateness of the method in view of the materials being tested, their potential applications, and the recommendation

8、s contained in Practice F748. 4.3 The only applicable limitation is the extract preparation. Refer to Sections 4.3 and 4.4 of Practice F619 for a description of this limitation. 5. Apparatus 5.1 CagesThere shall be one cage for each rabbit exposed to one extract liquid. Each rabbit shall be uniquely

9、 identied with this identity recorded. 5.2 SyringesSterilesyringes,notgreaterthan2mLinvolume,withaprecisionofnolessthan60.10mLshallbeused.Sterile needles of 21 to 26 gauge shall be used. 1 This practice is under the jurisdiction ofASTM Committee F04 on Medical and Surgical Materials and Devices and

10、is the direct responsibility of Subcommittee F04.16 on Biocompatibility Test Methods. Current edition approved Oct. 1, 2012March 1, 2013. Published October 2012March 2013. Originally approved in 1982. Last previous edition approved in 20072012 as F74998 (2007)(2012). e1 . DOI: 10.1520/F0749-98R12.10

11、.1520/F0749-13. 2 ForreferencedASTMstandards,visittheASTMwebsite,www.astm.org,orcontactASTMCustomerServiceatserviceastm.org.ForAnnualBookofASTMStandards volume information, refer to the standards Document Summary page on the ASTM website. This document is not anASTM standard and is intended only to

12、provide the user of anASTM standard an indication of what changes have been made to the previous version. Because it may not be technically possible to adequately depict all changes accurately, ASTM recommends that users consult prior editions as appropriate. In all cases only the current version of

13、 the standard as published by ASTM is to be considered the official document. Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States 16. Test Animals 6.1 RabbitsThe rabbits shall be healthy thin-skinned albino type, not previously used for a

14、ny test. Animal care shall be in accordancewithGuideforCareandUseofLaboratoryAnimals. 3 Rabbitswithsignicantscarsorwoundsarenotsuitableforthis test. For each extraction vehicle, a minimum of twothree rabbits are used in the test. If the results of the rst test are inconclusive, three more rabbits wi

15、ll be needed to complete the test with that extraction vehicle for one material. 6.1.1 During the test the rabbits shall be fed normally, with commercially available feed and tap water. 7. Sampling 7.1 Sample in accordance with Practice F619. 8. Sample and Test Specimen 8.1 Thesampleistheextractofth

16、etestarticle(thatis,plasticorothermaterial)exposedtotheextractionprocedure.Asaresult of the extraction in Practice F619, for each extraction vehicle there are available: (1) sample extract liquid, and (2) a blank extract liquid. These extract liquids are to be injected into the test animals within 2

17、4 h of the end of the extraction procedure. Record storage conditions if not used immediately after preparation. 8.1.1 There are usually four extract liquids prepared from two extraction vehicles available for test, those based on saline and vegetable oil. Samples based on other extraction vehicles

18、may be available, as described in Practice F619, or as required by the standard for the medical device. 8.2 The test specimen is the combination of the test site and 0.2 mL of the injected extract liquid.Atotal of 10 sites are to be injected with the sample extract liquid and 10 sites with the blank

19、 extract liquid. 9. Procedure 9.1 Preparation of RabbitsOn the day (no more than 24 h) before the test, closely clip the fur on the animals back on both sides of the spinal column over a sufficiently large test area.Avoid mechanical irritation and trauma. Remove loose hair by means ofavacuum.Theuseo

20、fadepilatoryagentthatdoesnotcauseskinirritationinplaceoforinadditiontoclippingmaybedesirable. Swab the skin slightly with diluted alcohol, and dry the skin prior to injection. 9.2 Agitateeachextractliquidvigorouslypriortowithdrawalofeachinjectiondosetoensureevendistributionoftheextracted matter. If

21、the extract liquid appears to contain particulates, record this and consider it when reporting the results. 9.3 Inject intracutaneously 0.2 mLof the sample extract liquid at ve sites on one side of each of two rabbits. Similarly, at ve other sites on the other side of each rabbit, inject 0.2 mL of t

22、he corresponding blank extract liquid. 9.4 Examinetheinjectedsites24,48,and72haftertheinjectionforgrossevidenceoftissuereaction,suchaserythema,edema, or necrosis. To facilitate the examination, swab the skin lightly with diluted alcohol, and clip the fur, if necessary. Rate the tissue reaction for a

23、ll ten sites of the sample and for the ve sites of the blank extract at each observation period for each type of tissue reaction. The rating scales for erythema and edema are given in Tables 1 and 2. 10. Interpretation of Results 10.1 Asample extract passes the test if each type of tissue reaction o

24、f the test and blank extracts are similar for all observation periods. 10.2 RetestIf either rabbit has a moderate or severe sample extract tissue reaction but the other does not, repeat the test using fresh extracts in three more rabbits. The sample extract passes if in this retest the tissue respon

25、ses for the sample extracts are not biologically different from those for the blank extract liquid. 4 3 The Guide for Care and Use of Laboratory Animals, Institute of LaboratoryAnimal Research Publication.Available from NationalAcademy Press, 500 Fifth St., NW, Lockbox 285, Washington, DC 20055. 4 B

26、iological Reactivity Tests, in Vivo, U. S. Pharmacopeia, Vol 26, Rockville, MD, 2002. TABLE 1 Severity Rating for Erythema Severity of Erythema Numerical Rating No erythema Very slight erythema (barely perceptible) 0 1 Well-dened erythema 2 Moderate to severe 3 Severe erythema (beet redness) to slig

27、ht eschar formation (injuries in depth) 4 F749 13 210.3 Aretest (see 10.2) requires that the extraction procedure be done a second time, since the extraction uids must be used within 24 h of the end of the extraction. 11. Report 11.1 Describe the sample that was extracted, including generic name, tr

28、ade name, manufacturers code, catalog number, date of manufacture, formulation, fabrication procedures or processes, etc., as appropriate. Describe the extraction vehicle and the conditions of the extraction (temperature and time). 11.2 Report the scores for each type of tissue reaction at each obse

29、rvation period as described in 10.1 for the test and control extracts. 11.3 If a retest was performed, report the data for that test, as in 11.2. 12. Precision and Bias 12.1 Intralaboratory and interlaboratory reproducibility have not been systematically determined. Reproducibility may be inferred f

30、rom previous round robin studies. 5,6 13. Keywords 13.1 acute toxicity tests; biocompatibility; intracutaneous injection; rabbits; test animals ASTM International takes no position respecting the validity of any patent rights asserted in connection with any item mentioned in this standard. Users of

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35、 ASTM website (www.astm.org/ COPYRIGHT/). 5 Brewer, John H., Toxicity Standards for Plastics, Bulletin of Parenteral Drug Association, Vol 19, 1965, pp. 2228. 6 Materials Science Toxicology Laboratories, University of Tennessee Center for the Health Sciences, Memphis, Tenn., Determination of Levels

36、of Chemical Purity for Biomaterials Used as Surgical Implants, Round Robin Evaluation of Primary Acute Toxicity Screening Protocols , Quarterly Report No. 1516, Part II, Contract No. FDA 223-73-5231,1978. TABLE 2 Severity Rating for Edema Severity of Edema A Numerical Rating No edema Very slight ede

37、ma (barely perceptible) 0 1 Slight edema (edges of area dened by denite raising) 2 Moderate edema (area raised approximately 1 mm) 3 Severe edema (area raised more than 1 mm and extending beyond area of injection) 4 A Edemaistissueswelling.Apparentswellingattributabletotheinjectionvehicleis not considered edema. F749 13 3