ASTM D6355-1998(2003) Standard Test Method for Human Repeat Insult Patch Testing of Medical Gloves《医用手套人重复损害修补试验的标准试验方法》.pdf

《ASTM D6355-1998(2003) Standard Test Method for Human Repeat Insult Patch Testing of Medical Gloves《医用手套人重复损害修补试验的标准试验方法》.pdf》由会员分享，可在线阅读，更多相关《ASTM D6355-1998(2003) Standard Test Method for Human Repeat Insult Patch Testing of Medical Gloves《医用手套人重复损害修补试验的标准试验方法》.pdf（6页珍藏版）》请在麦多课文档分享上搜索。

1、Designation: D 6355 98 (Reapproved 2003)Standard Test Method forHuman Repeat Insult Patch Testing of Medical Gloves1This standard is issued under the fixed designation D 6355; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revision, the yea

2、r 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.1. Scope1.1 This test method is designed to evaluate the potential ofglove materials under test to induce and elicit Type IV

3、 skinsensitization reactions (that is, allergic contact dermatitis) inhumans.1.2 This test method should be used by individuals experi-enced in or under the supervision of those experienced in theuse of good clinical practice procedures.1.3 During the performance of the Human Repeat InsultPatch Test

4、 (RIPT) for determining sensitization, investigatorsare confronted with skin responses that represent skin irritation(non-immunologic responses) or allergic contact dermatitis(ACD). The numerical scoring system for grading the intensityof both are similar and test facilities may vary in their scores

5、that describe intensities of allergic and irritant skin responses.The hallmark of a mild allergic contact dermatitis is a sustainedpalpable erythematous reaction. Delayed-type allergic contactreactions from patch tests have intensity characteristics thatfavor scores of higher values for longer perio

6、ds of time andtypically do not produce a minimal score (score of 1, ajust-perceptible erythema) for short durations (less than 48 h).It is the responsibility of the investigator to evaluate the scoresin light of irritant reactions so that the responses are allergic innature and not irritant. The inv

7、estigator should denote a finalscore as either due to contact allergy or irritation. Paragraphs9.5-9.5.5 describe a commonly used scoring system anddiscuss allergic and irritant responses in detail.1.4 The Draize RIPT was published in 1944 as an attempt todecrease the frequency ACD2. The test techni

8、ques at that timewere just being validated and this experimental design waslargely empiric3. The principle of the test is as follows:1.4.1 Multiple inductions of the study material at relativelynon or low irritancy levels,1.4.2 Approximately a two-week rest period, and1.4.3 A standard diagnostic cha

9、llenge of approximately 48 hand a delayed reading at approximately 96 h after patchapplication.1.5 In the intervening years, with further experimentationadded to this empiric approach, three additional principles havebeen learned:1.5.1 Increasing the concentration of the study material,1.5.2 Definin

10、g a no effect level (this is possible with onlyindividual ingredients and not the final study material), and1.5.3 The enhanced sensitivity and the use of occlusion(where occlusion would not ordinarily be present).1.6 In 1945, Henderson and Riley4demonstrated that a testpanel sample size of 30 000 su

11、bjects would have to beemployed to ensure statistically that there would be no morethan 0.1 % sensitization. If there are no allergic responses in atest panel of 200 subjects with exposures comparable to thoseof the population, then there could be as many as 1.5 allergicreactions per 100 users.1.7 A

12、ll medical devices must be safe and effective for theirintended use. Since medical devices such as gloves come incontact with human tissue, they should be tested for biocom-patibility in animals first. The human repeat insult patch test(RIPT) is one test that can be used to test rubber gloves for sk

13、insensitization to chemicals used in the manufacture of gloves.1.7.1 Since various forms of the RIPT exist, a singlestandardized test method that outlines the testing protocol,scoring system, and the criteria for skin sensitization should bedeveloped.1.8 This standard does not purport to address all

14、 of thesafety concerns, if any, associated with its use. It is theresponsibility of the user of this standard to establish appro-priate safety and health practices and determine the applica-bility of regulatory limitations prior to use.2. Terminology2.1 Definitions:1This test method is under the jur

15、isdiction of ASTM Committee D11 on Rubberand is the direct responsibility of Subcommittee D11.40 on Consumer RubberProducts.Current edition approved June 10, 2003. Published June 2003. Originallyapproved in 1998. Last previous edition approved in 1998 as D 6355 98.2Draize, J.H., Woodward, G., and Ca

16、lvery, H.O., “Methods for the Study ofIrritation and Toxicity of Substances Applied Topically to the Skin and MucousMembranes, Journal of Pharmacology and Experimental Therapeutics, Vol 83,1944, pp. 377-390.3Shelanski, H. A., and Shelanski, M. V., “A New Technique of Human PatchTest,” Proc. Sci. Sec

17、t. Toilet Goods Assoc., Vol 19, 1953, pp. 46-49.4Henderson, C. R., and Riley, E. C., “Certain Statistical Considerations in PatchTesting,” Journal of Investigative Dermatology, Vol 6, 1945, pp. 227-232.1Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-295

18、9, United States.2.1.1 allergen, na substance capable of causing an aller-gic reaction.2.1.2 allergic contact dermatitis (ACD), na Type IVdelayed-in-time dermatitis that is caused by skin contact witha hapten that evokes a cell-mediated (delayed-type hyersensi-tivity) immune response.2.1.3 allergic

19、contact dermatitis reaction, nan adverseimmune response following exposure to chemical (non-protein) allergens.2.1.4 antigen, nany substance that provokes an immuneresponse when introduced into the body.2.1.5 atopic dermatitis, nthe most common form ofchronic inflammatory dermatitis. Although immuno

20、logicmechanisms may play a role in producing this dermatitis, therole of any allergen in producing and sustaining this morpho-logically similar dermatitis is not proven or as clearly under-stood as classical allergic contact dermatitis.2.1.6 blister, na vesicle containing serum.2.1.7 bullae, nsynony

21、mous with blister.2.1.8 cell-mediated immunity, nthat portion of the im-mune system mediated by white blood cells called T-cells orT-lymphocytes.2.1.9 challenge test, na medical procedure used to iden-tify a substance to which a person is sensitive by deliberatelyre-exposing them to that substance i

22、n an attempt to reproducethe reaction.2.1.10 dermatitis, ninflammation of the skin evidenced byitching, redness, and various skin lesions.2.1.11 diagnostic patch tests, na form of skin testing inwhich suspected allergens are applied to the skin, covered, andobserved 48 to 96 h or more later to see i

23、f a reaction occurs.This test is often used to identify possible causes of allergiccontact dermatitis.2.1.12 eczema, nsynonymous with dermatitis.2.1.13 edema, nswelling caused by excessive infiltrationof fluid into the skin.2.1.14 erythema, nsynonymous with redness of the skin.2.1.15 immune response

24、, nthe activity of specialized cellsor their products against antigens and allergens introduced tothe body.2.1.16 immunize, vto render a patient immune from for-eign substances.2.1.17 induration, nhardening of a tissue due to edemaand cellular infiltration.2.1.18 inflammation, na basic response of t

25、he body toinjury, usually characterized by redness of the skin, warmth,swelling, and pain.2.1.19 irritation, na chemically induced dermatosis with-out immunological involvement.2.1.20 mast cells, ntissue cells that contain packets ofbiochemicals responsible for the symptoms of allergy. Whenallergens

26、 attach to IgE antibodies sitting on the surface of thesecells, a signal is sent, causing them to release these biochemicalmediators of allergy.2.1.21 mediators, nsoluble products of immune cells thatinteract and/or activate other parts of the immune system.2.1.22 mild irritant control, na substance

27、 that will pro-duce a minimally perceptible dermatitis.2.1.23 neutral control, na substance, such as water, thatthrough clinical usage, has not been found to be an allergen.2.1.24 papules, nsmall, solid red elevations of the skin.2.1.25 predictive patch test, na repeat insult patch test(RIPT) used a

28、s a toxicology test to determine the potential forACD.2.1.26 sensitive, vto expose to an antigen, provoking animmune response so that on re-exposure to that antigen, a moreadvanced secondary response occurs. Synonymous with im-munize.2.1.27 study material, na synthetic or natural polymermaterial use

29、d as a medical glove or as a part of a medicalglove.2.1.28 vesicles, nsmall circumscribed fluid-filled eleva-tions of the skin smaller than a blister.3. Summary of Test Method3.1 A general medical history of the study subjects shouldbe taken and include information on dermatologic conditionsand sens

30、itivities to specific compounds. Studies conducted inaccordance with this human RIPT protocol will employ aminimum of 200 study subjects. Prior to evaluating thematerial in a human RIPT, acceptable toxicology data shouldbe obtained. The sensitization potential of the study material isevaluated in a

31、test panel of a minimum group size of 200subjects. The study panel should include men and women. Theinduction phase of the human RIPT includes 10 multiple 48-h(72-h on weekends) patches at the same site typically on theupper back with no rest between repatching except for scoring.The patch site is g

32、raded for skin responses prior to eachsubsequent patch application. In the event of any significanterythema, the site of patch application should be moved toanother location to confirm the reaction. Following the comple-tion of the induction phase, there is approximately a 21 day restperiod to allow

33、 the development of latent sensitization. This isfollowed by two consecutive 48-h challenge patches applied tonaive sites. Responses are evaluated after the removal of eachconsecutive 48-h patch application. A minimum of two delayedskin site gradings is required to differentiate irritation fromsensi

34、tization reactions. If the results are equivocal, a secondchallenge, after the original challenge dermatitis has cleared,may be conducted to ensure that sensitization was not over-looked.4. Significance and Use4.1 This RIPT method assesses the potential of skin sensi-tization with a particular medic

35、al product by repeated topicalapplications to the skin of selected subjects. This is a procedurethat has the potential to detect many, but not all, sensitzers.This requires multiple applications to induce a cell-mediatedType IV immune response sufficient to cause an allergicreaction.4.2 In general,

36、the sensitization procedure requires 10 mul-tiple 48-h (72-h on weekends) applications of patches contain-ing the study material over a three-week induction phase.Induction is followed by approximately a 21 day rest phase toallow the development of any latent sensitization. StudyD 6355 98 (2003)2sub

37、jects are then challenged by the application of two consecu-tive 48-h patches of the study material to naive sites. Re-sponses are evaluated and graded after the removal of eachconsecutive 48-h patch application.4.3 Although this test method is a clinical method, it may beused as part of a risk anal

38、ysis to determine the potential forType IV allergic contact dermatitis.4.4 This test method assumes that good clinical practiceswill be utilized, including adequate training of practitioners.5. Interferences and Precautions5.1 During the course of the study, the area of the studysubjects where the p

39、atch is applied should not be bathed,showered, or washed. The patch area must stay dry. Wetpatches can be a source of mild irritation reactions.5.2 Caution: Patch testing can involve a certain risk to thesubject due to sensitization or raising of the level of sensitivityto the study material.6. Expe

40、rimental Plan6.1 Subject Inclusion/Selection Criteria6.1.1 Subjects ranging from 18 to 65 years.6.1.2 Subjects who complete a medical/personal historyform.6.1.3 Subjects who have read, understood, and signed aninformed consent agreement.6.1.4 Subjects should include both male and female.6.2 Subject

41、Exclusion/Rejection Criteria6.2.1 Subjects with skin disease that, in the opinion of theinvestigator, could interfere with the evaluation.6.2.2 Subjects taking medications that, in the opinion of theinvestigator, would interfere with the study.6.2.3 Subjects with clinically significant psoriasis, ec

42、zema,or atopic dermatitis.6.2.4 Subjects who are pregnant or become pregnant duringthe study.6.2.5 Subjects with known sensitivity to natural rubber andrubber chemicals.6.2.6 Subjects who have acquired a recent marked skintanning or sunburn that, in the opinion of the investigator,would interfere wi

43、th the study.6.2.7 Subjects who have undergone any type of sensitizationtesting within the last thirty days.6.2.8 Subjects who are lactating women.6.2.9 Subjects exogenously or endogenously immunosup-pressed.6.3 Study Group6.3.1 Sample Size:6.3.1.1 A minimum of 200 subjects will complete the study.6

44、.3.2 Clinical Sites:6.3.2.1 One clinical location with a minimum total samplesize of 200 subjects.6.3.2.2 The testing may be done in a single clinical locationbut avoiding extreme climatic conditions.7. Institutional Review and Informed Consent7.1 Institutional Review:7.1.1 The method for this study

45、 should be reviewed by anappropriate Institutional Review Board (IRB).7.2 Informed Consent:7.2.1 An informed consent document should be obtainedfrom each study subject prior to initiating the study.8. Study Materials and Patch8.1 The patch will be an adhesive bandage witha2by2-cmor larger Webril pad

46、 (or equivalent) affixed.8.2 All study materials should be applied in an amountproportionate to the size of the 2 by 2-cm or larger patch.8.3 A Neutral Control patch will be a adhesive bandage witha 2 by 2-cm or larger Webril pad (or equivalent) wetted with0.2 mL of distilled or deionized water.8.4

47、The study glove material should be applied so that theinside glove surface is exposed to the skin of the test subject.9. Study Design9.1 The human RIPT is performed to determine the poten-tial of the product for sensitization under conditions relative toanticipated consumer exposure.9.2 Patch Site:9

48、.2.1 Patches should be applied to the upper back area,either to the right or left of the midline. (The arm may be usedas an alternative patch site to the back area.)9.2.2 The upper back, either to the right or left of themidline, is the most common site used for patch testing. Thisarea has been pref

49、erred because of its larger, more uniformsurface; it is more accommodating to multiple tests. For manyvolunteer subjects, testing at this site is less obtrusive. How-ever, there are occasions when the upper arm or forearm maybe the preferred site. There is no data that supports thesuperiority of one of these skin sites over another for inducingexperimental sensitization.9.3 Study Description:9.3.1 Induction Phase:9.3.1.1 The induction phase of the RIPT includes 10 mul-tiple 48-h (72-h on weekends) patches at a single site on theupper back with no rest betwee