ASTM F1408-97(2002)e1

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e1
Designation:F1408–97 (Reapproved 2002)
Standard Practice for
Subcutaneous Screening Test for Implant Materials
This standard is issued under the fixed designation F 1408; 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 (e) indicates an editorial change since the last revision or reapproval.
e NOTE—Footnote 3 was editorially corrected in November 2002.
1. Scope Implant Applications (UNS R56401)
F 138 Specification for Wrought 18Chromium-14Nickel-
1.1 This practice covers a short-term testing method to
2.5Molybdenum Stainless Steel Bar and Wire for Surgical
screen the subcutaneous tissue reaction to metallic or other
Implants (UNS S31673)
implant candidate materials in small laboratory animals. The
F 648 Specification for Ultra-High-Molecular-Weight Poly-
material may be dense or porous. The tissue reactions will be
ethylene Powder and Fabricated Form for Surgical Im-
evaluated in comparison to those evoked by control materials
plants
that are accepted as clinical implant materials.
F 763 Practice for Short-Term Screening of Implant Mate-
1.2 This practice, along with other appropriate biological
rials
tests (including other ASTM test methods), may be used to
F 981 Practice for Assessment of Compatibility of Bio-
assessthebiocompatibilityofcandidatematerialsforuseinthe
materials for Surgical Implants With Respect to Effect of
fabrication of devices for clinical application. It may be also
Materials on Muscle and Bone
applied to evaluate the effect of special surface textures and
preparations of known materials.
3. Summary of Practice
1.3 This experimental protocol is not designed to provide a
3.1 Under strict aseptic conditions, specimens of the candi-
comprehensive assessment of the systemic toxicity, carcinoge-
date and control materials are implanted subcutaneously in the
nicity, teratogenicity, or mutagenicity of the material.
neck of mice (or other suitable animals). After one, three, and
1.4 The values stated in SI units are to be regarded as the
nine weeks the animals are anesthetized and the test samples
standard.
are excised with an intact tissue envelope. On histologic
1.5 This standard does not purport to address all of the
sections the tissue reactions to the candidate materials are
safety concerns, if any, associated with its use. It is the
compared with the tissue response to clinically accepted
responsibility of the user of this standard to establish appro-
control materials.
priate safety and health practices and determine the applica-
bility of regulatory limitations prior to use.
4. Significance and Use
2. Referenced Documents 4.1 This practice is a guideline for a short-term screening
test for the evaluation of the tissue response to materials that
2.1 ASTM Standards:
may be selected for implantation in the human body. This test
F 67 Specification for Unalloyed Titanium for Surgical
may be performed prior to longterm testing (for example,
Implant Applications (UNS R50250, UNS R50400, UNS
2 Practice F 981) to eliminate unsuitable candidate materials
R50550, UNS R50700)
early and to save further animal testing.
F 75 Specification for Cobalt-28Chromium-6Molybdenum
4.2 This practice may be used to detect toxic effects of
Alloy Castings and Casting Alloy for Surgical Implants
2 materials in general (seeAppendix X1). However, it is particu-
(UNS R30075)
larly suitable for the testing of materials that are intended to
F 86 Practice for Surface Preparation and Marking of Me-
2 have contact with subcutaneous tissues or soft tissues in
tallic Surgical Implants
general. For materials intended to be inserted specifically into
F 136 Specification for Wrought Titanium-6Aluminum-
muscle tissues, Practice F 763 should be considered as a short
4Vanadium ELI (Extra Low Interstitial) Alloy for Surgical
term test method.
4.3 The suggested implant specimens are cylindrical. A
This practice is under the jurisdiction ofASTM Committee F-4 on Medical and special grooved type of cylinder may be used (see Fig. X2.1 of
Surgical Materials and Devices and is the direct responsibility of Subcommittee
Appendix X2) to allow tissue interlocking that could keep the
F04.16 on Biocompatibility Test Methods.
implant in place and minimize tissue irritation through motion
Current edition approved November 10, 1997. Published June 1998. Originally
at the interface that otherwise could contribute to increased
published as F 1408 - 92. Last previous edition F 1408 - 92 (1996).
Annual Book of ASTM Standards, Vol 13.01.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.
e1
F1408–97 (2002)
variance of the results. In case ungrooved cylinders are used If more than one specimen is implanted in larger test hosts, at
(see Fig. X1.2 of Appendix X2), probable motion at the least four animals should be used per material and time period.
implant/tissue interface must be taken into account. Control 6.5 Conditioning—The cleaning, sterilization, and packag-
cylinders should be shaped like the test cylinders. ing should be the same as used for implantation in the human
patient. After surface preparation and sterilization the implant
4.4 The type of surface preparation of the specimens can
affect the tissue reaction, therefore the preparation procedure specimens should be protected from surface alterations and
should be noted in the report. The test may be used to compare contamination and should be handled with non-metallic for-
the effect of different surface structures or conditions of the ceps when appropriate. When plastified forceps are used, be
same material or to assess the effect of various treatments of sure that no plastic material is transferred to the implant
modifications of a material. surface.
7. Procedure
5. Test Animals and Sites
7.1 Implantation:
5.1 Mice of an established strain, (preferably females), are
7.1.1 Implant the specimens under sterile conditions in
usedastesthosts.Thetestmaybeadaptedtoothersuitabletest
anesthetized animals. The incision site is remote from the
animals (for example, rats).
implantation site to prevent infection around the implant. In
5.2 The implant specimens of control and candidate mate-
mice, makea1cm long incision above the sacrum and prepare
rials are inserted subcutaneously in the neck of the host.
a subcutaneous tunnel toward the neck.
5.3 One implant is inserted per mouse. Therefore, the
7.1.2 Pushtheimplantthroughthetunnelandpositionatthe
number of animals is identical with the number of test
neck. In some distance of the implant close the tunnel with
specimens. If rats or other larger suitable animals are used,
three stitches with a thread of a non-metallic suture material to
more than one test specimen may be implanted, but the
preventmovingoftheimplant.Thenclosetheincision.(Donot
implants should never be allowed to come in contact with each
place the implant directly underneath the incision to avoid
other. If animals other than mice are large enough, cylinders of
infection.)
thecandidateandcontrolmaterialmaybeimplantedseparately
7.1.3 Keep the individually marked animals in standard
at the right and the left side of the neck in one animal.
cagesthatcomplywithcurrentanimalprotectionrequirements.
Keep mice up to three or four weeks in individual cages.
6. Implant Specimens
7.2 Post-Operative Care—Care of the animals should be in
6.1 Specimen Design—Cylinders of 7 mm length and 4 mm
accordance with accepted standards as outlined in the Guide
diameter are prepared for implantation in mice. Special speci-
for the Care and Use of Laboratory Animals.
mens with two grooves are designed corresponding to the
7.2.1 Carefully observe each animal during the period of
figures in Appendix X2. If larger animal hosts are used, the
assay, and report any abnormal clinical findings.
implant dimensions may be increased proportionally. If it is
7.2.2 Ifinfectionorinjuryofthetestimplantsiteinvalidates
impossible to prepare specimens of this kind, the specimen
the results, replace the animal so that the number of retrieved
configuration used must be described fully in the report.
implants will be at least that of the schedule.
Implant specimens from the candidate and control material
7.2.3 Ifananimaldiespriortotheexpecteddateofsacrifice,
should always have the same dimensions.
autopsyitanddeterminethecauseofdeath.Replacetheanimal
6.2 Selection of Control Materials—Recommended metals
ifthecauseofdeathisunrelatedtothetestprocedureorthetest
for use as control materials include those given in Specifica-
material. Include the test animal in the assay of data if the
tions F 67, F 75, F 136, and F 138. However, for specific
cause of death is related to the procedure or test material.
applications any metal of known compatibility and standard-
7.3 Sacrifice and Implant Retrieval:
ized as implant material may be employed as control material
7.3.1 Sacrifice the animals after one, three, and nine weeks.
for comparison. To study adverse tissue reactions, a non-
If longer time intervals are of interest, mice may be kept up to
compatible material like copper may be used as a positive
24 weeks. Examine and report the status of the health of the
control material.Asuitable polymeric control material like the
animals prior to euthanasia.
polyethylene USP negative control plastic, RS, or UHMWPE
7.3.2 At sacrifice, record any gross abnormalities of color or
(see Specification F 648) may be used.
consistency observed on the tissues surrounding the implant.
6.3 Specimen Surface—The surface of specimens from
Remove each implant with an intact tissue envelope. If the
prospective implant materials should be treated in the same
tissue envelope was damaged during the excision, such
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