ASTM F2808-10
(Test Method)Standard Test Method for Performing Behind-the-Knee (BTK) Test for Evaluating Skin Irritation Response to Products and Materials That Come Into Repeated or Extended Contact with Skin
Standard Test Method for Performing Behind-the-Knee (BTK) Test for Evaluating Skin Irritation Response to Products and Materials That Come Into Repeated or Extended Contact with Skin
SIGNIFICANCE AND USE
This test method is intended to assess a combination of inherent chemical irritation and mechanical irritation for products and materials expected to come into contact with the skin. It is a comparative approach whereby the potential irritation of a test material is compared to that of a reference material similar in form and composition. The reference material should have a known safety and irritation profile.
SCOPE
1.1 The Behind-the-Knee (BTK) method, using the popliteal fossa of human volunteers as a test site, simultaneously evaluates the inherent chemical irritation, and the potential for mechanical irritation of substrates and products that are designed to come into repeated or extended close contact with the skin (see validation references 1-7). This is a bilateral test comparing a test material to a reference material with a known safety profile.
1.2 This test method shall be used by qualified health care professionals experienced in good clinical practice (GCP) procedures.
1.3 This test method can be performed using human subjects on either intact or compromised skin. Testing should be performed on intact skin for test substrates or products expected to have contact with normal, intact skin, or for direct comparison to products with a known skin irritation profile. Testing can be performed on compromised skin for test substrates or products that may commonly come into contact with damaged skin (for example, skin with diaper rash, or chapped skin) or skin that is expected to be hydrated.
1.4 Visual scoring of erythema and dryness is performed by a trained skin grader on a pre-defined scale.
1.5 Prior to use in this test, materials shall undergo overall favorable biocompatibility testing consistent with the approach outlined in protocol Practice F748 or ISO 10993-1:2009. As a part of this series of testing, irritation per Practice F719 or ISO 10993-10 shall be conducted.
1.6 The values stated in inch-pound units are to be regarded as standard. No other units of measurement are included in this standard.
1.7 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.
General Information
Relations
Standards Content (Sample)
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: F2808 − 10
Standard Test Method for
Performing Behind-the-Knee (BTK) Test for Evaluating Skin
Irritation Response to Products and Materials That Come
Into Repeated or Extended Contact with Skin
This standard is issued under the fixed designation F2808; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision.Anumber in parentheses indicates the year of last reapproval.A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope 1.7 This standard does not purport to address all of the
safety concerns, if any, associated with its use. It is the
1.1 The Behind-the-Knee (BTK) method, using the
responsibility of the user of this standard to establish appro-
popliteal fossa of human volunteers as a test site, simultane-
priate safety and health practices and determine the applica-
ously evaluates the inherent chemical irritation, and the poten-
bility of regulatory limitations prior to use.
tialformechanicalirritationofsubstratesandproductsthatare
designed to come into repeated or extended close contact with
2. Referenced Documents
the skin (see validation references 1-7). This is a bilateral test
2.1 ASTM Standards:
comparing a test material to a reference material with a known
D6355Test Method for Human Repeat Insult Patch Testing
safety profile.
of Medical Gloves
1.2 This test method shall be used by qualified health care
F719Practice for Testing Biomaterials in Rabbits for Pri-
professionals experienced in good clinical practice (GCP)
mary Skin Irritation
procedures.
F748PracticeforSelectingGenericBiologicalTestMethods
for Materials and Devices
1.3 This test method can be performed using human sub-
jects on either intact or compromised skin. Testing should be
2.2 ISO Standards:
performed on intact skin for test substrates or products ex- ISO 10993-1:2009 Biological Evaluation of Medical
pected to have contact with normal, intact skin, or for direct
Devices—Part 1: Evaluation and Testing Within a Risk
comparison to products with a known skin irritation profile. Management Process
Testing can be performed on compromised skin for test
ISO 10993-10Biological Evaluation of Medical Devices—
substrates or products that may commonly come into contact Part 10: Tests for Irritation and Delayed-type Hypersensi-
with damaged skin (for example, skin with diaper rash, or tivity
chapped skin) or skin that is expected to be hydrated.
3. Terminology
1.4 Visual scoring of erythema and dryness is performed by
3.1 Definitions:
a trained skin grader on a pre-defined scale.
3.1.1 chemical irritation, n—irritation caused by a physi-
1.5 Prior to use in this test, materials shall undergo overall
ological response to the chemical nature of a material. Such
favorablebiocompatibilitytestingconsistentwiththeapproach
physiological responses may include: oxidation or reduction
outlined in protocol Practice F748 or ISO 10993-1:2009.As a
reactions, dehydration, disruption of the keratin ultra-structure
partofthisseriesoftesting,irritationperPracticeF719orISO
or direct injury to cellular macromolecules or organelles.
10993-10 shall be conducted.
3.1.2 compromised skin, n—skin that is treated with re-
1.6 The values stated in inch-pound units are to be regarded
peated application of surgical tape prior to the first sample
asstandard.Nootherunitsofmeasurementareincludedinthis
application.
standard.
3.1.3 edema, n—observable swelling from abnormal accu-
mulation of fluid in connective tissue.
ThistestmethodisunderthejurisdictionofASTMCommitteeF04onMedical
andSurgicalMaterialsandDevicesandisthedirectresponsibilityofSubcommittee For referenced ASTM standards, visit the ASTM website, www.astm.org, or
F04.16 on Biocompatibility Test Methods. contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM
Current edition approved Oct. 15, 2010. Published November 2010. DOI: Standards volume information, refer to the standard’s Document Summary page on
10.1520/F2808–10. the ASTM website.
2 4
Theboldfacenumbersinparenthesesrefertothelistofreferencesattheendof Available fromAmerican National Standards Institute (ANSI), 25 W. 43rd St.,
this standard. 4th Floor, New York, NY 10036, http://www.ansi.org.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F2808 − 10
3.1.4 erythema, n—redness of the skin. 6.2 The use of lotions, powders, creams, or skin care
products in the skin area at the test sites during the course of
3.1.5 mechanical irritation, n—irritation caused by move-
thestudymayimpactthestudyresults.Inaddition,shavingthe
ment and friction of products intended to remain in contact
skin behind the knee, exposing the test sites to tanning or the
with the skin for extended periods of time.
sun, or swimming or hot tub use during study participation
3.1.6 popliteal fossa, n—the area at the back of the knee.
should not be permitted, since these practices and activities
3.1.7 reference material, n—a material similar in form and
may produce low levels of skin irritation in some persons.
composition to the test material.The reference material should
6.3 Anti-inflammatory medications may interfere with the
have a known safety and irritation profile.
normal development of the skin irritation reaction and should
3.1.8 skin grades, n—visual assessments of erythema and
not be used during the study.
dryness according to a defined scale (see 10.3).
6.4 Normal showering or bathing cannot be allowed during
3.1.9 test material, n—any material or product expected to
the sample application of 6 h per day, but can be allowed
come into contact with skin.
duringthe18heachdaywhenthetestsamplesarenotinplace.
3.1.10 trained skin grader, n—personnel who have been
6.5 Some persons will experience some degree of skin
trainedtoreliablyrecognizeerythemaanddrynessreactionsby
irritation at the test sites. In addition, some persons may
using reference examples, and by performing side-by-side
experience slight discomfort from the manner in which the
scoring with an experienced skin grader.
samples are applied (that is, an elastic knee band). In most
cases, these effects are anticipated to be reversible when
4. Summary of Test Method
sample application concludes.
4.1 Samples are applied to the back of the knee using an
elastic knee band or brace. As the subjects go about their 7. Apparatus
everyday activities, normal movements generate friction be-
7.1 An artificial light source, with a 100 W incandescent
tween the test sample and the skin at the test site, thereby
daylight blue bulb, is used to illuminate the application areas
addingtheelementofmechanicalirritation.Thus,theBTKtest
for erythema grading and an illuminated 10× magnifying lens
protocol evaluates a combination of mechanical irritation and
is used to grade dryness.
the inherent chemical irritation potential of materials and
products that come into contact with the skin.
8. Reagents and Materials
4.2 This is a randomized, controlled, double blind study in
8.1 Elastic knee bands or braces are used to hold the
which both the subjects and skin grader are unaware of the
samples in place.
treatmentassignments.Testandreferencematerialsareapplied
8.2 Test materials include substrates and products that are
for 6 h per day, for 5 days. Skin reactions are graded for
designed to come into repeated or extended close contact with
erythema and dryness prior to the first sample application (that
theskin.Theappropriatereferencesampleisasimilarmaterial
is, at baseline), each morning prior to subsequent sample
or product that has been demonstrated through biocompatibil-
applications, and upon the removal of the sample at the end of
ity testing to be a non-irritant.
each period.
8.3 If testing is to be conducted on compromised skin, an
4.3 Test materials are applied, once each test day to normal,
appropriate surgical tape is required.
intact skin to evaluate potential reactions to products that
normally come into contact with intact skin. To evaluate
9. Hazards
potential reactions to products that normally come into contact
9.1 No specific hazards have been identified for this test
withdamagedskin,theskincanbecompromisedbyusingtape
protocol.However,ifanyofthetestmaterialstestedshouldfall
stripping prior to the first sample application.
under biohazard then all used test materials should be handled
and discarded by the test site staff following Biohazard
5. Significance and Use
Standard Operating Procedures (SOPs).
5.1 This test method is intended to assess a combination of
inherent chemical irritation and mechanical irritation for prod-
10. Calibration and Standardization
ucts and materials expected to come into contact with the skin.
10.1 No calibration of specific equipment is required.
It is a comparative approach whereby the potential irritation of
10.2 Skin graders shall be trained to recognize the degrees
a test material is compared to that of a reference material
of severity of the irritation reactions described in the grading
similarinformandcomposition.Thereferencematerialshould
scales given in Appendix X7.
have a known safety and irritation profile.
10.3 The Skin Irritation Grading Scales for Erythema and
6. Interferences and Precautions
Dryness (Appendix X7) are similar to those scales used by
6.1 Possible protocol deviations that could interfere with or contract testing facilities in a variety of skin testing protocols,
affect the outcome of the study include the fit of the elastic including single patch tests placed on the upper arm, multiple
knee band and the activity level of the subjects. As in any patch tests in cumulative irritation testing, forearm controlled
clinical study, adherence to the protocol conditions will offset application testing, nasal irritation, and Human Repeat Insult
any potential confounding issues. PatchTesting(asoutlinedinTestMethodD6355).Skingraders
F2808 − 10
should be trained to recognize erythema and dryness reactions (3)Psoriasis, eczema, skin cancer, or any active dermatitis
by performing side-by-side scoring of patch tests or BTK tests thatcouldpotentiallyinterferewithinterpretationoftestresults
with an experienced skin grader until the trainee can reliably
at the test sites;
recognize the reactions. (4)Use of corticosteroids (oral or topical) or other types of
drugs that may interfere with the normal development of
11. Institutional Review and Informed Consent
irritation, inflammation, or immune reactions;
(5)Participation in a behind-the-knee study within the last
11.1 Institutional Review:
four weeks;
11.1.1 The method for this study and qualification of per-
(6)Known irritancy or discomfort in the area behind the
sons conducting the study shall be reviewed by an appropriate
knee which would prevent the subject from wearing a knee
Institutional Review Board (IRB).
brace for 6 h each day during study participation;
11.2 Informed Consent:
(7)Current pregnancy or lactation (self-reported);
11.2.1 An informed consent document should be read,
(8)Diabetes or kidney disease (self-reported) which may
understood, and signed by the subjects prior to initiating the
be associated with potential circulatory problems;
study.
(9)Heart or circulatory disease (including blood clots)
(self-reported)whichmaybeexacerbatedbywearinganelastic
12. Procedure
knee band for 6 h each day during study participation;
12.1 Subjects—Each experiment should include a general
(10)Leg varicosities which would interfere with the sub-
sample size calculation done by a statistician to determine the
ject’s wearing a knee brace for 6 h each day during study
number of subjects in the study (see 13.3).Asufficient number
participation;
of subjects should be recruited give the study sufficient power
(11)Arthritis in the lower extremities;
to achieve a statistically significant difference between the
(12)Known allergies to tape(s) and/or adhesives;
reference and test samples, and to allow for a drop out rate
(13)History of edema in the lower extremities;
consistent with the norms for the test facility. In the course of
(14)Kneecircumferencegreaterthan21in.(since21in.is
recruitment, demographic information (age, sex, ethnicity,
the maximum size that can be accommodated by many
height, and weight) should be collected on each subject.
commercial elastic knee bands).
Subjects should be healthy adults between 18 and 65 years of
12.1.2 Once eligibility is confirmed, the areas behind the
age, who meet the inclusion/exclusion criteria and preferably
knees are screened for cuts, scratches, rashes, sunburn, acne,
with Fitzpatrick skin type I to IV mixture.
abrasions,scartissue,tattoos,oranyotherconditionthatcould
12.1.1 Specific inclusion/exclusion criteria are as follows
prevent a clear assessment of their skin during the test portion
(see Appendix X1):
of the study.
12.1.1.1 Inclusion Criteria—Subjects who:
(1)Have read, understood, and signed the informed con- 12.1.3 At the enrollment visit, subjects are fitted for the
sent;
elastic knee band based on the manufacturer’s recommenda-
(2)Are at least 18 years old;
tion. The subject is provided with two identical, unused knee
(3)Are no more than 65 years old;
bands to wear throughout the study. However, if a subject is
(4)Are in general good health (self-declared);
having a degree of discomfort which he or she finds
(5)Are Fitzpatrick skin type I to IV (see Appendix X2);
intolerable, adjustments in the size can be made, as long as the
(6)Agree to refrain from using lotions, creams, powders,
identicaladjustmentismadetobothtestsites(thatis,rightand
or other skin preparations on the skin in the area behind the
left knee bands). The knee bands are placed in a separate bag
knee during participation in the study;
for each subject, and labeled in a manner that will identify the
(7)Agree to refrain from shaving the skin in the area
subject. One brand of knee bands should be used for all
behind the knee during participation in the study;
subjects. A sample worksheet is provided in Appendix X3.
(8)Agree to refrain from swimming or hot tub use during
12.1.4 Subjects receive an instruction sheet asking them to
participation in the study;
refrain from using lotions, powders, creams, or skin care
(9)Agree to refrain from fitness training during sample
products in the area behind their knees during their participa-
application;
tion in the study (see sample in Appendix X4). Additionally,
(10)Agree to refrain from tanning or sun exposure to the
they shall be instructed to refrain from shaving the area behind
test area during participation in the study;
their knees, fitness training during sample application, tanning
(11)Agree to refrain from
...
Questions, Comments and Discussion
Ask us and Technical Secretary will try to provide an answer. You can facilitate discussion about the standard in here.