ASTM F1408-97
(Practice)Standard Practice for Subcutaneous Screening Test for Implant Materials
Standard Practice for Subcutaneous Screening Test for Implant Materials
SCOPE
1.1 This practice provides 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 the standard.
1.5 This standard does not purport to address all of the safety problems, 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NOTICE: This standard has either been superseded and replaced by a new version or discontinued.
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Designation: F 1408 – 97
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.
1. Scope F 763 Practice for Short-Term Screening of Implant Mate-
rials
1.1 This practice covers a short-term testing method to
F 981 Practice for Assessment of Compatibility of Bio-
screen the subcutaneous tissue reaction to metallic or other
materials for Surgical Implants With Respect to Effect of
implant candidate materials in small laboratory animals. The
Materials on Muscle and Bone
material may be dense or porous. The tissue reactions will be
evaluated in comparison to those evoked by control materials
3. Summary of Practice
that are accepted as clinical implant materials.
3.1 Under strict aseptic conditions, specimens of the candi-
1.2 This practice, along with other appropriate biological
date and control materials are implanted subcutaneously in the
tests (including other ASTM test methods), may be used to
neck of mice (or other suitable animals). After one, three, and
assess the biocompatibility of candidate materials for use in the
nine weeks the animals are anesthetized and the test samples
fabrication of devices for clinical application. It may be also
are excised with an intact tissue envelope. On histologic
applied to evaluate the effect of special surface textures and
sections the tissue reactions to the candidate materials are
preparations of known materials.
compared with the tissue response to clinically accepted
1.3 This experimental protocol is not designed to provide a
control materials.
comprehensive assessment of the systemic toxicity, carcinoge-
nicity, teratogenicity, or mutagenicity of the material.
4. Significance and Use
1.4 The values stated in SI units are to be regarded as the
4.1 This practice is a guideline for a short-term screening
standard.
test for the evaluation of the tissue response to materials that
1.5 This standard does not purport to address all of the
may be selected for implantation in the human body. This test
safety concerns, if any, associated with its use. It is the
may be performed prior to longterm testing (for example,
responsibility of the user of this standard to establish appro-
Practice F 981) to eliminate unsuitable candidate materials
priate safety and health practices and determine the applica-
early and to save further animal testing.
bility of regulatory limitations prior to use.
4.2 This practice may be used to detect toxic effects of
2. Referenced Documents materials in general (see Appendix X1). However, it is particu-
larly suitable for the testing of materials that are intended to
2.1 ASTM Standards:
have contact with subcutaneous tissues or soft tissues in
F 67 Specification for Unalloyed Titanium for Surgical
2 general. For materials intended to be inserted specifically into
Implant Applications
muscle tissues, Practice F 763 should be considered as a short
F 75 Specification for Cast Cobalt-ChromiumMolybdenum
2 term test method.
Alloy for Surgical Implant Applications
4.3 The suggested implant specimens are cylindrical. A
F 86 Practice for Surface Preparation and Marking of Me-
2 special grooved type of cylinder may be used (see Fig. X2.1 of
tallic Surgical Implants
Appendix X2) to allow tissue interlocking that could keep the
F 136 Specification for Wrought Titanium 6Al-4V ELI
2 implant in place and minimize tissue irritation through motion
Alloy for Surgical Implant Applications
at the interface that otherwise could contribute to increased
F 138 Specification for Stainless Steel Bar and Wire for
2 variance of the results. In case ungrooved cylinders are used
Surgical Implants (Special Quality)
(see Fig. X1.2 of Appendix X2), probable motion at the
F 648 Specification for Ultra-High-Molecular-Weight Poly-
implant/tissue interface must be taken into account. Control
ethylene Powder and Fabricated Form for Surgical Im-
2 cylinders should be shaped like the test cylinders.
plants
4.4 The type of surface preparation of the specimens can
affect the tissue reaction, therefore the preparation procedure
This practice is under the jurisdiction of ASTM Committee F-4 on Medical and
should be noted in the report. The test may be used to compare
Surgical Materials and Devices and is the direct responsibility of Subcommittee
the effect of different surface structures or conditions of the
F04.16 on Biocompatibility Test Methods.
Current edition approved November 10, 1997. Published June 1998. Originally
same material or to assess the effect of various treatments of
published as F 1408 - 92. Last previous edition F 1408 - 92 (1996).
modifications of a material.
Annual Book of ASTM Standards, Vol 13.01.
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NOTICE: This standard has either been superseded and replaced by a new version or discontinued.
Contact ASTM International (www.astm.org) for the latest information.
F 1408
5. Test Animals and Sites 7. Procedure
7.1 Implantation:
5.1 Mice of an established strain, (preferably females), are
7.1.1 Implant the specimens under sterile conditions in
used as test hosts. The test may be adapted to other suitable test
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 Push the implant through the tunnel and position at the
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
prevent moving of the implant. Then close the incision. (Do not
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.)
the candidate and control material may be implanted separately
7.1.3 Keep the individually marked animals in standard
at the right and the left side of the neck in one animal.
cages that comply with current animal protection requirements.
Keep mice up to three or four weeks in individual cages.
6. Implant Specimens
7.2 Post-Operative Care:
6.1 Specimen Design— Cylinders of 7 mm length and 4 mm
7.2.1 Care of the animals should be in accordance with
diameter are prepared for implantation in mice. Special speci-
accepted standards as outlined in the Guide for the Care and
mens with two grooves are designed corresponding to the Use of Laboratory Animals.
figures in Appendix X2. If larger animal hosts are used, the
7.2.2 Carefully observe each animal during the period of
implant dimensions may be increased proportionally. If it is assay, and report any abnormal clinical findings.
impossible to prepare specimens of this kind, the specimen
7.2.3 If infection or injury of the test implant site invalidates
configuration used must be described fully in the report. the results, replace the animal so that the number of retrieved
Implant specimens from the candidate and control material
implants will be at least that of the schedule.
should always have the same dimensions.
7.2.4 If an animal dies prior to the expected date of sacrifice,
autopsy it and determine the cause of death. Replace the animal
6.2 Selection of Control Materials—Recommended metals
if the cause of death is unrelated to the test procedure or the test
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. A suitable 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 should
manner as the implant intended for clinical application in the
be reported. Transfer the tissue specimen as soon as possible in
human patient. Depending on the particular issue, the control
a fixing agent that does not interfere with the implant material
specimens should have either a surface condition as it is
and its probable degradation products.
normally used for clinical applications or a surface condition
most similar to that of the tested candidate material. For
8. Histologic Evaluation
preparation of metallic materials Practice F 86 should be
8.1 Histological Preparation:
considered.
8.1.1 In general, standard laboratory practices for histologi-
6.4 Numbers of Test and Control Implants—Per each time
cal pr
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