ASTM F749-1998(2007)e1 Standard Practice for Evaluating Material Extracts by Intracutaneous Injection in the Rabbit《兔子皮内注射评定材料抽提物》.pdf

1、Designation: F 749 98 (Reapproved 2007)e1Standard Practice forEvaluating Material Extracts by Intracutaneous Injection inthe Rabbit1This standard is issued under the fixed designation F 749; the number immediately following the designation indicates the year oforiginal adoption or, in the case of re

2、vision, the year of last revision. A number in parentheses indicates the year of last reapproval. Asuperscript epsilon (e) indicates an editorial change since the last revision or reapproval.e1NOTEFormatting and grammar were corrected editorially throughout in April 2007.1. Scope1.1 This practice is

3、 a nonspecific, acute toxicity test used tohelp determine the biocompatibility of materials used inmedical devices.1.2 The liquids injected into the rabbits are those obtainedby Practice F 619 where the extraction vehicles are saline,vegetable oil, or other liquids simulating human body fluids.1.3 T

4、his practice is one of several developed for theassessment of the biocompatibility of materials. Practice F 748may 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 as thestandard.2. Referenc

5、ed Documents2.1 ASTM Standards:2F 619 Practice for Extraction of Medical PlasticsF 748 Practice for Selecting Generic Biological Test Meth-ods for Materials and Devices3. Summary of Practice3.1 The extract liquid is prepared in accordance with Prac-tice F 619. The extraction vehicles are saline and

6、vegetable oil,or other extraction vehicles can be used, as described inPractice F 619. The extract liquid is injected into rabbits andthe animals are observed at regular intervals for 72 h forerythema, edema, and necrosis.4. Significance and Use4.1 This practice is to be used to help assess the bioc

7、om-patibility of materials used in medical 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 v

8、iew of the materials beingtested, their potential applications, and the recommendationscontained in Practice F 748.4.3 The only applicable limitation is the extract preparation.Refer to Sections 4.3 and 4.4 of Practice F 619 for a descriptionof this limitation.5. Apparatus5.1 CagesThere shall be one

9、 cage for each rabbit exposedto one extract liquid. Each rabbit will 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 Animals

10、6.1 RabbitsThe rabbits shall be healthy 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

11、 rabbits are used in the test. If the results 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.7. Sampling7.1 S

12、ample in accordance with Practice F 619.8. 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 F 619, for eachextraction vehicle there are available: (1) sample ext

13、ract liquid,1This practice is under the jurisdiction ofASTM Committee F04 on Medical andSurgical Materials and Devices and is the direct responsibility of SubcommitteeF04.16 on Biocompatibility Test Methods.Current edition approved Feb. 1, 2007. Published February 2007. Originallyapproved in 1982. L

14、ast previous edition approved in 2002 as F 749 98 (2002)e2.2For 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.3T

15、he Guide for Care and Use of Laboratory Animals, Institute of LaboratoryAnimal Research Publication. Available from National Academy Press, 500 FifthSt., NW, Lockbox 285, Washington, DC 20055.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United

16、States.and (2) a blank 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

17、 available for test, those based on salineand vegetable oil. Samples based on other extraction vehiclesmay be available, as described in Practice F 619, 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 li

18、quid. A total of 10 sites 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 lar

19、ge test area.Avoid mechanical 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 Agi

20、tate each extract liquid 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 extractliqu

21、id at five sites on one 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

22、, or necrosis. To facilitate 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 fo

23、rerythema and edema are 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 b

24、ut the other does not, 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-

25、dure be done a second 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, catalog num-ber, date of manufacture, formulation, fabrication proceduresor proce

26、sses, etc., as appropriate. 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 dat

27、a for that test,as in 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; rabb

28、its; test animals4“ Biological 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 for

29、the Health Sciences, Memphis, 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 Erythem

30、aSeverity of ErythemaNumericalRatingNo 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 edem

31、a (barely perceptible)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 vehicleis not c

32、onsidered edema.F 749 98 (2007)e12ASTM International takes no position respecting the validity of any patent rights asserted in connection with any item mentionedin this standard. Users of this standard are expressly advised that determination of the validity of any such patent rights, and the risko

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35、ur views known to the ASTM 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).F 749 98 (2007)e13