Standard Practice for Evaluating Material Extracts by Intracutaneous Injection in the Rabbit

SIGNIFICANCE 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 designed 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 recommendations 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.
SCOPE
1.1 This practice is a nonspecific, acute toxicity test used to help determine the biocompatibility of materials used in medical devices.  
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 fluids.  
1.3 This practice is one of several developed for the assessment of the biocompatibility of materials. Practice F748 may provide guidance for the selection of appropriate methods for testing materials for a specific 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.

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Publication Date
30-Sep-2012
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ASTM F749-98(2012) - Standard Practice for Evaluating Material Extracts by Intracutaneous Injection in the Rabbit
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NOTICE: This standard has either been superseded and replaced by a new version or withdrawn.
Contact ASTM International (www.astm.org) for the latest information
Designation: F749 − 98(Reapproved 2012)
Standard Practice for
Evaluating Material Extracts by Intracutaneous Injection in
the Rabbit
ThisstandardisissuedunderthefixeddesignationF749;thenumberimmediatelyfollowingthedesignationindicatestheyearoforiginal
adoption or, in the case of revision, the year of last revision.Anumber in parentheses indicates the year of last reapproval.Asuperscript
epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope 4. Significance and Use
1.1 This practice is a nonspecific, acute toxicity test used to 4.1 This practice is to be used to help assess the biocom-
help determine the biocompatibility of materials used in patibility of materials used in medical devices. It is an acute
medical devices. toxicological test designed to detect the presence of injurious
leachable substances.
1.2 The liquids injected into the rabbits are those obtained
by Practice F619 where the extraction vehicles are saline, 4.2 This practice may not be appropriate for all types of
vegetable oil, or other liquids simulating human body fluids. implant applications. The user is cautioned to consider the
appropriateness of the method in view of the materials being
1.3 This practice is one of several developed for the
tested, their potential applications, and the recommendations
assessment of the biocompatibility of materials. Practice F748
contained in Practice F748.
may provide guidance for the selection of appropriate methods
for testing materials for a specific application. 4.3 The only applicable limitation is the extract preparation.
Refer to Sections 4.3 and 4.4 of Practice F619 for a description
1.4 The values stated in SI units are to be regarded as
of this limitation.
standard. No other units of measurement are included in this
standard.
5. Apparatus
2. Referenced Documents
5.1 Cages—There shall be one cage for each rabbit exposed
to one extract liquid. Each rabbit shall be uniquely identified
2.1 ASTM Standards:
with this identity recorded.
F619 Practice for Extraction of Medical Plastics
F748 PracticeforSelectingGenericBiologicalTestMethods
5.2 Syringes—Sterile syringes, not greater than 2 mL in
for Materials and Devices
volume, with a precision of no less than 60.10 mL shall be
used. Sterile needles of 21 to 26 gauge shall be used.
3. Summary of Practice
6. Test Animals
3.1 The extract liquid is prepared in accordance with Prac-
tice F619. The extraction vehicles are saline and vegetable oil,
6.1 Rabbits—The rabbits shall be healthy thin-skinned al-
or other extraction vehicles can be used, as described in
binotype,notpreviouslyusedforanytest.Animalcareshallbe
PracticeF619.Theextractliquidisinjectedintorabbitsandthe
in accordance with Guide for Care and Use of Laboratory
animals are observed at regular intervals for 72 h for erythema,
Animals. Rabbits with significant scars or wounds are not
edema, or necrosis.
suitableforthistest.Foreachextractionvehicle,aminimumof
two rabbits are used in the test. If the results of the first test are
ThispracticeisunderthejurisdictionofASTMCommitteeF04onMedicaland inconclusive, three more rabbits will be needed to complete the
Surgical Materials and Devices and is the direct responsibility of Subcommittee
test with that extraction vehicle for one material.
F04.16 on Biocompatibility Test Methods.
6.1.1 During the test the rabbits shall be fed normally, with
Current edition approved Oct. 1, 2012. Published October 2012. Originally
ε1
commercially available feed and tap water.
approved in 1982. Last previous edition approved in 2007 as F749 – 98 (2007) .
DOI: 10.1520/F0749-98R12.
For referenced ASTM standards, visit the ASTM website, www.astm.org, or
contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM The Guide for Care and Use of Laboratory Animals, Institute of Laboratory
Standards volume information, refer to the standard’s Document Summary page on Animal Research Publication. Available from National Academy Press, 500 Fifth
the ASTM website. St., NW, Lockbox 285, Washington, DC 20055.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F749 − 98 (2012)
TABLE 1 Severity Rating for Erythema
7. Sampling
Numerical
7.1 Sample in accordance with Practice F619. Severity of Erythema
Rating
No erythema 0
8. Sample and Test Specimen
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
8.1 The sample is the extract of the test article (that is,
Moderate to severe 3
plastic or other material) exposed to the extraction procedure.
Severe erythema (beet redness) to slight eschar formation 4
(injuries in depth)
As a result 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
TABLE 2 Severity Rating for Edema
injected into the test animals within 24 h of the end of the
Numerical
A
extraction procedure. Record storage conditions if not used
Severity of Edema
Rating
immediately after preparation.
No edema 0
8.1.1 There are usually four extract liquids prepared from
Very slight edema (barely perceptible) 1
two extraction vehicles available for test, those based on saline Slight edema (edges of area defined by definite raising) 2
Moderate edema (area raised approximately 1 mm) 3
and vegetable oi
...

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