ASTM F719-1981(2012) Standard Practice for Testing Biomaterials in Rabbits for Primary Skin Irritation《测试生物材料对兔子原发性皮肤剌激性的标准实施规程》.pdf

1、Designation: F719 81 (Reapproved 2012)Standard Practice forTesting Biomaterials in Rabbits for Primary Skin Irritation1This standard is issued under the fixed designation F719; the number immediately following the designation indicates the year of originaladoption or, in the case of revision, the ye

2、ar 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 covers a procedure by which the irritancyof a biomaterial may be assessed through contact with abr

3、adedand intact skin of rabbits.1.2 The results of this practice depend upon the effective-ness with which contact between the skin and the test materialis established and maintained. Because of the operator tech-nique included in performing this test, it is important that thetest be performed by per

4、sonnel with appropriate training.1.3 The values stated in SI units are to be regarded asstandard. No other units of measurement are included in thisstandard.1.4 This standard does not purport to address all of thesafety concerns, if any, associated with its use. It is theresponsibility of the user o

5、f this standard to establish appro-priate safety and health practices and determine the applica-bility of regulatory limitations prior to use.2. Referenced Documents2.1 ASTM Standards:2F619 Practice for Extraction of Medical Plastics3. Summary of Practice3.1 Exposure of skin to the test material is

6、accomplished bymeans of a patch test technique employing two intact and twoabraded sites on the back of each of six albino rabbits. The skinis clipped free of hair one day prior to testing. The testsubstance is applied using 0.5 mL for liquids, 0.5 g for solidsor semisolids, and a 2.5 by 2.5-cm squa

7、re patch for films. Afterapplication, each test site is covered with a 2.5 by 2.5-cm gauzeflat, and the entire trunk is occluded with a polyethylene sleeve.After 24 h, the sleeve, flat, and test material are removed, andtest sites are evaluated for erythema and edema.4. Significance and Use4.1 Mater

8、ials that are to be in contact with the skin shouldnot cause irritation to the skin. Since it is probably thesubstances leached from a material that cause the irritation, thispractice provides for direct material-skin contact testing or forskin exposure to the liquid extract of the test material. Th

9、erationale for this rabbit test is that it is a comparatively quickand inexpensive method which, through use over the years, hasbecome a generally accepted method.5. Materials and Manufacture5.1 Young New Zealand Albino Rabbits,5.2 Gauze Flats, 2.5 by 2.5-cm,5.3 Polyethylene Sleeves, extra clear, an

10、d5.4 Adhesive Tape,12-in.6. Test Specimen6.1 The test specimen may be one of three forms:6.1.1 Test 0.5 mL of liquids or saline extract liquids ob-tained in accordance with Practice F619.6.1.2 Test 0.5 g of solids or semisolids.6.1.3 Test films 2.5 by 2.5 cm.NOTE 1A vehicle control for liquids is re

11、quired because of thepotential for false positives due to skin temperature changes whenhandling rabbits. Positive controls may be used to validate the test method.The use of 5 % procaine HCl as a positive control is suggested.36.2 The pH of the solutions should be measured andreported, if appropriat

12、e.7. Procedure7.1 Preparation of Test Animals:7.1.1 Twenty-four hours before the test, clip the hair fromthe backs of the animals so as to expose two test areas on eachside of the spine, which are 10 cm apart.7.1.2 To obtain more effective contact between the skin andthe test substance, it may be ne

13、cessary to use a non-irritatingdepilatory agent. This test method may be used to ensure thatthe depilatory agent is non-irritating.1This practice is under the jurisdiction ofASTM Committee F04 on Medical andSurgical Materials and Devices and is the direct responsibility of SubcommitteeF04.16 on Bioc

14、ompatibility Test Methods.Current edition approved Oct. 1, 2012. Published October 2012. Originallyapproved in 1981. Last previous edition approved in 2007 as F719 81 (2007)1.DOI: 10.1520/F0719-81R12.2For referenced ASTM standards, visit the ASTM website, www.astm.org, orcontact ASTM Customer Servic

15、e at serviceastm.org. For Annual Book of ASTMStandards volume information, refer to the standards Document Summary page onthe ASTM website.3H. H. Draize, Appraisal of the Safety of Chemicals in Foods, Drugs, andCosmetics, 1965, p. 46.Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700,

16、West Conshohocken, PA 19428-2959. United States17.1.3 Test sites may be designated as two on each side of thespine. Alternatively, the area may be divided into quadrantswith test and control substances applied to each quadrant.7.2 Test Procedure:7.2.1 Wipe the exposed area of the back with alcohol.7

17、.2.2 Using a sterile blade, abrade two of the four sites bymoving the blade at right angles to the cutting surface in ascraping motion to create a denuded area of skin.Alternatively,make four epidermal incisions (which penetrate the stratumcorneum but not the dermis), with two perpendicular to theot

18、her two.7.2.3 Place the appropriate amount of the test material, asdescribed in 6.1, on one intact and one abraded or incised site.Place the control material on the other abraded and intact sites.7.2.4 Immediately occlude the sites by placing gauze flatson the test and control sites. Secure the patc

19、hes with adhesivetape.7.2.5 Tightly wrap the animals trunk with a clear polyeth-ylene sleeve.7.3 Test Site Examination and Scoring:7.3.1 Remove the polyethylene sleeve, gauze flats, test andcontrol materials, and any excess test or control liquids 24 hafter applying the test and control substances.

20、Use alcoholsolutions for removing excess liquids.7.3.2 Using the criteria of Table 1, score test sites forerythema and edema 1 h after removal.7.3.3 Rescore test sites for erythema and edema in accor-dance with Table 1 at 24 and 48 h after removal . Take care todistinguish test site erythema from mi

21、nor skin temperaturechanges.NOTE 2There is a possibility of infection associated with skinabrasion. Since infection would cause the same symptoms (erythema andedema) as would primary irritation, it is essential to ensure that thereaction is not due to infection. Any reaction at the control sites cou

22、ld bean indication of infection. If infection is suspected, the test should berepeated with a new animal, and the test substance cultured.8. Interpretation and Calculation of Results8.1 Score abraded and intact test sites for erythema andedema in accordance with Table 1.8.2 The primary irritation in

23、dex (PII) for each test animaland substance is the total of the abraded (incised) and intactskin scores for erythema and edema at 1, 24, and 48 h afterremoval, divided by six. The average primary irritation index isequal to the sum of the PIIs for each substance for all testanimals divided by the nu

24、mber of test animals.9. Report9.1 The report should contain a description of the testmaterial, batch or lot number, vehicles, and extraction proce-dure used.9.2 Report the pH value of test solution and vehicle solutionif appropriate.9.3 Report test data for erythema and edema in accordancewith Fig.

25、1.10. Keywords10.1 acute toxicity tests; biocompatibility; rabbits; skinirritation; test animalsTABLE 1 Scoring Criteria for Test ReactionsReaction Description ScoreErythema(ER)Erythema and EscharNo erythemaVery slight erythema (barely perceptible)01Well-defined erythema (pale red in color) 2Moderat

26、e to severe erythema (red and areawell defined)3Severe erythema (beet redness to slighteschar formation)4Edema (ED) Edema FormationNo edemaVery slight (barely perceptible)01Slight edema (edges of area well defined bydefinite raising)2Moderate edema (edges raisedapproximately 1 mm)3Severe edema (rais

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