ASTM F749-1998(2012) 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

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1、Designation: F749 98 (Reapproved 2012)Standard Practice forEvaluating Material Extracts by Intracutaneous Injection inthe Rabbit1This standard is issued under the fixed designation F749; the number immediately following the designation indicates the year of originaladoption or, in the case of revisi

2、on, the year of last revision. A number in parentheses indicates the year of last reapproval. A superscriptepsilon () indicates an editorial change since the last revision or reapproval.1. Scope1.1 This practice is a nonspecific, acute toxicity test used tohelp determine the biocompatibility of mate

3、rials used inmedical devices.1.2 The liquids injected into the rabbits are those obtainedby Practice F619 where the extraction vehicles are saline,vegetable oil, or other liquids simulating human body fluids.1.3 This practice is one of several developed for theassessment of the biocompatibility of m

4、aterials. Practice F748may provide guidance for the selection of appropriate methodsfor testing materials for a specific application.1.4 The values stated in SI units are to be regarded asstandard. No other units of measurement are included in thisstandard.2. Referenced Documents2.1 ASTM Standards:2

5、F619 Practice for Extraction of Medical PlasticsF748 Practice for Selecting Generic Biological Test Methodsfor Materials and Devices3. Summary of Practice3.1 The extract liquid is prepared in accordance with Prac-tice F619. The extraction vehicles are saline and vegetable oil,or other extraction veh

6、icles can be used, as described inPractice F619. The extract liquid is injected into rabbits and theanimals are observed at regular intervals for 72 h for erythema,edema, or necrosis.4. Significance and Use4.1 This practice is to be used to help assess the biocom-patibility of materials used in medi

7、cal devices. It is an acutetoxicological test designed to detect the presence of injuriousleachable substances.4.2 This practice may not be appropriate for all types ofimplant applications. The user is cautioned to consider theappropriateness of the method in view of the materials beingtested, their

8、 potential applications, and the recommendationscontained 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 descriptionof this limitation.5. Apparatus5.1 CagesThere shall be one cage for each rabbit exposedto one extra

9、ct liquid. Each rabbit shall be uniquely identifiedwith this identity recorded.5.2 SyringesSterile syringes, not greater than 2 mL involume, with a precision of no less than 60.10 mL shall beused. Sterile needles of 21 to 26 gauge shall be used.6. Test Animals6.1 RabbitsThe rabbits shall be healthy

10、thin-skinned al-bino type, not previously used for any test.Animal care shall bein accordance with Guide for Care and Use of LaboratoryAnimals.3Rabbits with significant scars or wounds are notsuitable for this test. For each extraction vehicle, a minimum oftwo rabbits are used in the test. If the re

11、sults of the first test areinconclusive, three more rabbits will be needed to complete thetest with that extraction vehicle for one material.6.1.1 During the test the rabbits shall be fed normally, withcommercially available feed and tap water.1This practice is under the jurisdiction ofASTM Committe

12、e F04 on Medical andSurgical Materials and Devices and is the direct responsibility of SubcommitteeF04.16 on Biocompatibility Test Methods.Current edition approved Oct. 1, 2012. Published October 2012. Originallyapproved in 1982. Last previous edition approved in 2007 as F749 98 (2007)1.DOI: 10.1520

13、/F0749-98R12.2For referenced ASTM standards, visit the ASTM website, www.astm.org, orcontact ASTM Customer Service at serviceastm.org. For Annual Book of ASTMStandards volume information, refer to the standards Document Summary page onthe ASTM website.3The Guide for Care and Use of Laboratory Animal

14、s, Institute of LaboratoryAnimal Research Publication. Available from National Academy Press, 500 FifthSt., NW, Lockbox 285, Washington, DC 20055.Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States17. Sampling7.1 Sample in accordance with

15、 Practice F619.8. Sample and Test Specimen8.1 The sample is the extract of the test article (that is,plastic or other material) exposed to the extraction procedure.As a result of the extraction in Practice F619, for eachextraction vehicle there are available: (1) sample extract liquid,and (2) a blan

16、k extract liquid. These extract liquids are to beinjected into the test animals within 24 h of the end of theextraction procedure. Record storage conditions if not usedimmediately after preparation.8.1.1 There are usually four extract liquids prepared fromtwo extraction vehicles available for test,

17、those based on salineand vegetable oil. Samples based on other extraction vehiclesmay be available, as described in Practice F619, or as requiredby the standard for the medical device.8.2 The test specimen is the combination of the test site and0.2 mL of the injected extract liquid. A total of 10 si

18、tes are tobe injected with the sample extract liquid and 10 sites with theblank extract liquid.9. Procedure9.1 Preparation of RabbitsOn the day (no more than 24 h)before the test, closely clip the fur on the animals back on bothsides of the spinal column over a sufficiently large test area.Avoid mec

19、hanical irritation and trauma. Remove loose hair bymeans of a vacuum. The use of a depilatory agent that does notcause skin irritation in place of or in addition to clipping maybe desirable. Swab the skin slightly with diluted alcohol, anddry the skin prior to injection.9.2 Agitate each extract liqu

20、id vigorously prior to with-drawal of each injection dose to ensure even distribution of theextracted matter. If the extract liquid appears to containparticulates, record this and consider it when reporting theresults.9.3 Inject intracutaneously 0.2 mL of the sample extractliquid at five sites on on

21、e side of each of two rabbits. Similarly,at five other sites on the other side of each rabbit, inject 0.2 mLof the corresponding blank extract liquid.9.4 Examine the injected sites 24, 48, and 72 h after theinjection for gross evidence of tissue reaction, such aserythema, edema, or necrosis. To faci

22、litate the examination,swab the skin lightly with diluted alcohol, and clip the fur, ifnecessary. Rate the tissue reaction for all ten sites of the sampleand for the five sites of the blank extract at each observationperiod for each type of tissue reaction. The rating scales forerythema and edema ar

23、e given in Tables 1 and 2.10. Interpretation of Results10.1 A sample extract passes the test if each type of tissuereaction of the test and blank extracts are similar for allobservation periods.10.2 RetestIf either rabbit has a moderate or severesample extract tissue reaction but the other does not,

24、 repeat thetest using fresh extracts in three more rabbits. The sampleextract passes if in this retest the tissue responses for thesample extracts are not biologically different from those for theblank extract liquid.410.3 A retest (see 10.2) requires that the extraction proce-dure be done a second

25、time, since the extraction fluids must beused within 24 h of the end of the extraction.11. Report11.1 Describe the sample that was extracted, includinggeneric name, trade name, manufacturers code, catalognumber, date of manufacture, formulation, fabrication proce-dures or processes, etc., as appropr

26、iate. Describe the extractionvehicle and the conditions of the extraction (temperature andtime).11.2 Report the scores for each type of tissue reaction ateach observation period as described in 10.1 for the test andcontrol extracts.11.3 If a retest was performed, report the data for that test,as in

27、11.2.12. Precision and Bias12.1 Intralaboratory and interlaboratory reproducibilityhave not been systematically determined. Reproducibility maybe inferred from previous round robin studies.5,613. Keywords13.1 acute toxicity tests; biocompatibility; intracutaneousinjection; rabbits; test animals4“ Bi

28、ological Reactivity Tests, in Vivo,” U. S. Pharmacopeia, Vol 26,Rockville, MD, 2002.5Brewer, John H., “Toxicity Standards for Plastics,” Bulletin of Parenteral DrugAssociation, Vol 19, 1965, pp. 2228.6Materials Science Toxicology Laboratories, University of Tennessee Center forthe Health Sciences, M

29、emphis, Tenn., “Determination of Levels of Chemical Purityfor Biomaterials Used as Surgical Implants,” Round Robin Evaluation of PrimaryAcute Toxicity Screening Protocols , Quarterly Report No. 1516, Part II, ContractNo. FDA 223-73-5231, 1978.TABLE 1 Severity Rating for ErythemaSeverity of ErythemaN

30、umericalRatingNo erythemaVery slight erythema (barely perceptible)01Well-defined erythema 2Moderate to severe 3Severe erythema (beet redness) to slight eschar formation(injuries in depth)4TABLE 2 Severity Rating for EdemaSeverity of EdemaANumericalRatingNo edemaVery slight edema (barely perceptible)

31、01Slight edema (edges of area defined by definite raising) 2Moderate edema (area raised approximately 1 mm) 3Severe edema (area raised more than 1 mm andextending beyond area of injection)4AEdema is tissue swelling.Apparent swelling attributable to the injection vehicle isnot considered edema.F749 9

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35、M Committee on Standards, at the address shown below.This standard is copyrighted by ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959,United States. Individual reprints (single or multiple copies) of this standard may be obtained by contacting ASTM at the aboveaddress or at 610-832-9585 (phone), 610-832-9555 (fax), or serviceastm.org (e-mail); or through the ASTM website(www.astm.org). Permission rights to photocopy the standard may also be secured from the ASTM website (www.astm.org/COPYRIGHT/).F749 98 (2012)3