ASTM F1408-97(2013)
(Practice)Standard Practice for Subcutaneous Screening Test for Implant Materials
Standard Practice for Subcutaneous Screening Test for Implant Materials
SIGNIFICANCE AND USE
4.1 This practice is a guideline for a short-term screening test for the evaluation of the tissue response to materials that may be selected for implantation in the human body. This test may be performed prior to longterm testing (for example, Practice F981) to eliminate unsuitable candidate materials early and to save further animal testing.
4.2 This practice may be used to detect toxic effects of materials in general (see Appendix X1). However, it is particularly suitable for the testing of materials that are intended to have contact with subcutaneous tissues or soft tissues in general. For materials intended to be inserted specifically into muscle tissues, Practice F763 should be considered as a short term test method.
4.3 The suggested implant specimens are cylindrical. A special grooved type of cylinder may be used (see Fig. X2.1 of Appendix X2) to allow tissue interlocking that could keep the implant in place and minimize tissue irritation through motion at the interface that otherwise could contribute to increased variance of the results. In case ungrooved cylinders are used (see Fig. X1.2 of Appendix X2), probable motion at the implant/tissue interface must be taken into account. Control cylinders should be shaped like the test cylinders.
4.4 The type of surface preparation of the specimens can affect the tissue reaction, therefore the preparation procedure should be noted in the report. The test may be used to compare the effect of different surface structures or conditions of the same material or to assess the effect of various treatments of modifications of a material.
SCOPE
1.1 This practice covers a short-term testing method to screen the subcutaneous tissue reaction to metallic or other implant candidate materials in small laboratory animals. The material may be dense or porous. The tissue reactions will be evaluated in comparison to those evoked by control materials that are accepted as clinical implant materials.
1.2 This practice, along with other appropriate biological tests (including other ASTM test methods), may be used to assess the biocompatibility of candidate materials for use in the fabrication of devices for clinical application. It may be also applied to evaluate the effect of special surface textures and preparations of known materials.
1.3 This experimental protocol is not designed to provide a comprehensive assessment of the systemic toxicity, carcinogenicity, teratogenicity, or mutagenicity of the material.
1.4 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.
1.5 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatory limitations prior to use.
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Standards Content (Sample)
NOTICE: This standard has either been superseded and replaced by a new version or withdrawn.
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Designation: F1408 − 97 (Reapproved 2013)
Standard Practice for
Subcutaneous Screening Test for Implant Materials
This standard is issued under the fixed designation F1408; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope F86 Practice for Surface Preparation and Marking of Metal-
lic Surgical Implants
1.1 This practice covers a short-term testing method to
F136 Specification for Wrought Titanium-6Aluminum-
screen the subcutaneous tissue reaction to metallic or other
4Vanadium ELI (Extra Low Interstitial)Alloy for Surgical
implant candidate materials in small laboratory animals. The
Implant Applications (UNS R56401)
material may be dense or porous. The tissue reactions will be
F138 Specification for Wrought 18Chromium-14Nickel-
evaluated in comparison to those evoked by control materials
2.5Molybdenum Stainless Steel Bar and Wire for Surgical
that are accepted as clinical implant materials.
Implants (UNS S31673)
1.2 This practice, along with other appropriate biological
F648 Specification for Ultra-High-Molecular-Weight Poly-
tests (including other ASTM test methods), may be used to
ethylene Powder and Fabricated Form for Surgical Im-
assessthebiocompatibilityofcandidatematerialsforuseinthe
plants
fabrication of devices for clinical application. It may be also
F763 Practice for Short-Term Screening of Implant Materi-
applied to evaluate the effect of special surface textures and
als
preparations of known materials.
F981 Practice for Assessment of Compatibility of Biomate-
1.3 This experimental protocol is not designed to provide a rials for Surgical Implants with Respect to Effect of
Materials on Muscle and Bone
comprehensive assessment of the systemic toxicity,
carcinogenicity, teratogenicity, or mutagenicity of the material.
3. Summary of Practice
1.4 The values stated in SI units are to be regarded as
3.1 Under strict aseptic conditions, specimens of the candi-
standard. No other units of measurement are included in this
date and control materials are implanted subcutaneously in the
standard.
neck of mice (or other suitable animals). After one, three, and
1.5 This standard does not purport to address all of the
nine weeks the animals are anesthetized and the test samples
safety concerns, if any, associated with its use. It is the
are excised with an intact tissue envelope. On histologic
responsibility of the user of this standard to establish appro-
sections the tissue reactions to the candidate materials are
priate safety and health practices and determine the applica-
compared with the tissue response to clinically accepted
bility of regulatory limitations prior to use.
control materials.
2. Referenced Documents
4. Significance and Use
2.1 ASTM Standards:
4.1 This practice is a guideline for a short-term screening
F67 Specification for Unalloyed Titanium, for Surgical Im-
test for the evaluation of the tissue response to materials that
plant Applications (UNS R50250, UNS R50400, UNS
may be selected for implantation in the human body. This test
R50550, UNS R50700)
may be performed prior to longterm testing (for example,
F75 Specification for Cobalt-28 Chromium-6 Molybdenum
Practice F981) to eliminate unsuitable candidate materials
Alloy Castings and Casting Alloy for Surgical Implants
early and to save further animal testing.
(UNS R30075)
4.2 This practice may be used to detect toxic effects of
materials in general (see Appendix X1). However, it is particu-
ThispracticeisunderthejurisdictionofASTMCommitteeF04onMedicaland
larly suitable for the testing of materials that are intended to
Surgical Materials and Devices and is the direct responsibility of Subcommittee
F04.16 on Biocompatibility Test Methods.
have contact with subcutaneous tissues or soft tissues in
Current edition approved Oct. 1, 2013. Published October 2013. Originally
general. For materials intended to be inserted specifically into
approved in 1992. Last previous edition approved in 2008 as F1408 - 97 (2008).
muscle tissues, Practice F763 should be considered as a short
DOI: 10.1520/F1408-97R13.
For referenced ASTM standards, visit the ASTM website, www.astm.org, or term test method.
contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM
4.3 The suggested implant specimens are cylindrical. A
Standards volume information, refer to the standard’s Document Summary page on
the ASTM website. special grooved type of cylinder may be used (see Fig. X2.1 of
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F1408 − 97 (2013)
Appendix X2) to allow tissue interlocking that could keep the most similar to that of the tested candidate material. For
implant in place and minimize tissue irritation through motion preparation of metallic materials Practice F86 should be
at the interface that otherwise could contribute to increased considered.
variance of the results. In case ungrooved cylinders are used
6.4 Numbers of Test and Control Implants—Per each time
(see Fig. X1.2 of Appendix X2), probable motion at the
period, at least six implant specimens of each candidate and
implant/tissue interface must be taken into account. Control
control material should be evaluated in mice (one per mouse).
cylinders should be shaped like the test cylinders.
If more than one specimen is implanted in larger test hosts, at
least four animals should be used per material and time period.
4.4 The type of surface preparation of the specimens can
affect the tissue reaction, therefore the preparation procedure
6.5 Conditioning—The cleaning, sterilization, and packag-
should be noted in the report. The test may be used to compare
ing should be the same as used for implantation in the human
the effect of different surface structures or conditions of the
patient. After surface preparation and sterilization the implant
same material or to assess the effect of various treatments of
specimens should be protected from surface alterations and
modifications of a material.
contamination and should be handled with non-metallic for-
ceps when appropriate. When plastified forceps are used, be
5. Test Animals and Sites sure that no plastic material is transferred to the implant
surface.
5.1 Mice of an established strain, (preferably females), are
usedastesthosts.Thetestmaybeadaptedtoothersuitabletest
7. Procedure
animals (for example, rats).
7.1 Implantation:
5.2 The implant specimens of control and candidate mate-
7.1.1 Implant the specimens under sterile conditions in
rials are inserted subcutaneously in the neck of the host.
anesthetized animals. The incision site is remote from the
implantation site to prevent infection around the implant. In
5.3 One implant is inserted per mouse. Therefore, the
mice, makea1cm long incision above the sacrum and prepare
number of animals is identical with the number of test
a subcutaneous tunnel toward the neck.
specimens. If rats or other larger suitable animals are used,
7.1.2 Pushtheimplantthroughthetunnelandpositionatthe
more than one test specimen may be implanted, but the
neck. In some distance of the implant close the tunnel with
implants should never be allowed to come in contact with each
three stitches with a thread of a non-metallic suture material to
other. If animals other than mice are large enough, cylinders of
preventmovingoftheimplant.Thenclosetheincision.(Donot
the candidate and control material may be implanted separately
place the implant directly underneath the incision to avoid
at the right and the left side of the neck in one animal.
infection.)
7.1.3 Keep the individually marked animals in standard
6. Implant Specimens
cagesthatcomplywithcurrentanimalprotectionrequirements.
6.1 Specimen Design—Cylinders of 7 mm length and 4 mm Keep mice up to three or four weeks in individual cages.
diameter are prepared for implantation in mice. Special speci-
7.2 Post-Operative Care—Care of the animals should be in
mens with two grooves are designed corresponding to the
accordance with accepted standards as outlined in the Guide
figures in Appendix X2. If larger animal hosts are used, the
for the Care and Use of Laboratory Animals.
implant dimensions may be increased proportionally. If it is
7.2.1 Carefully observe each animal during the period of
impossible to prepare specimens of this kind, the specimen
assay, and report any abnormal clinical findings.
configuration used must be described fully in the report.
7.2.2 Ifinfectionorinjuryofthetestimplantsiteinvalidates
Implant specimens from the candidate and control material
the results, replace the animal so that the number of retrieved
should always have the same dimensions.
implants will be at least that of the schedule.
7.2.3 Ifananimaldiespriortotheexpecteddateofsacrifice,
6.2 Selection of Control Materials—Recommended metals
autopsyitanddeterminethecauseofdeath.Replacetheanimal
for use as control materials include those given in Specifica-
ifthecauseofdeathisunrelatedtothetestprocedureorthetest
tions F67, F75, F136, and F138. However, for specific appli-
material. Include the test animal in the assay of data if the
cations any metal of known compatibility and standardized as
cause of death is related to the procedure or test material.
implant material may be employed as control material for
comparison. To study adverse tissue reactions, a non-
7.3 Sacrifice and Implant Retrieval:
compatible material like copper may be used as a positive
7.3.1 Sacrifice the animals after one, three, and nine weeks.
control material.Asuitable polymeric control material like the
If longer time intervals are of interest, mice may be kept up to
polyethylene USP negative control plastic, RS, or UHMWPE
24 weeks. Examine and report the status of the health of the
(see Specification F648) may be used.
animals prior to euthanasia.
7.3.2 At sacr
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