EN ISO 10993-10:2010

Biological evaluation of medical devices - Part 10: Tests for irritation and skin sensitization (ISO 10993-10:2010)

ISO 10993-10:2010 describes the procedure for the assessment of medical devices and their constituent materials with regard to their potential to produce irritation and skin sensitization.
ISO 10993-10:2010 includes:
pretest considerations for irritation, including in silico and in vitro methods for dermal exposure;
details of in vivo (irritation and sensitization) test procedures;
key factors for the interpretation of the results.
Instructions are given for the preparation of materials specifically in relation to the above tests and several special irritation tests are described for application of medical devices in areas other than skin.

Biologische Beurteilung von Medizinprodukten - Teil 10: Prüfung auf Irritation und Hautsensibilisierung (ISO 10993-10:2010)

Dieser Teil der ISO 10993 beschreibt das Verfahren für die Beurteilung von Medizinprodukten und ihren
Bestandteilen hinsichtlich ihres Potentials, eine Irritation und eine Hautsensibilisierung hervorzurufen.
Dieser Teil der ISO 10993 enthält:
a) vor der Prüfung durchzuführende Überlegungen hinsichtlich einer Irritation, einschließlich In-silico- und Invitro-
Verfahren zur dermalen Exposition;
b) Einzelheiten zur Durchführung von In-vivo-Prüfungen (Irritation und Sensibilisierung);
c) Schlüsselfaktoren für die Interpretation der Ergebnisse.
Anhang A enthält Anweisungen für die spezielle Vorbereitung von Materialien im Zusammenhang mit den
vorstehend angeführten Prüfungen. In Anhang B sind mehrere spezielle Prüfungen auf Irritation bei der
Anwendung von Medizinprodukten in anderen Bereichen als der Haut beschrieben.

Évaluation biologique des dispositifs médicaux - Partie 10: Essais d'irritation et de sensibilisation cutanée (ISO 10993-10:2010)

L'ISO 10993-10:2010 décrit le mode opératoire pour l'évaluation du potentiel des dispositifs médicaux et de leurs matériaux constitutifs à provoquer une irritation et une sensibilisation de la peau.
L'ISO 10993-10:2010 comprend
des considérations préalablement aux essais relatives à l'irritation, y compris des méthodes in silico et in vitro d'exposition dermique,
des informations détaillées relatives aux procédures d'essai in vivo (irritation et sensibilisation), et
des facteurs clés pour l'interprétation des résultats.
Des instructions sont fournies en vue de la préparation des matériaux, notamment pour les essais précités et plusieurs essais d'irritation spéciaux pour l'application de dispositifs médicaux dans des zones autres que la peau.

Biološko ovrednotenje medicinskih pripomočkov - 10. del: Preskusi draženja in preobčutljivosti kože (ISO 10993-10:2010)

Ta del ISO 10993 opisuje postopek za ocenjevanje medicinskih pripomočkov in materialov, iz katerih so narejeni, z vidika njihovega potenciala za povzročanje draženja in preobčutljivosti kože. Ta del ISO 10993 vključuje: a) obravnavo pred preskusom glede draženja, vključno z metodami izpostavljenost kože in silico ter in vitro; b) podrobnosti preskusnih postopkov in vivo (za draženje in preobčutljivost), in; c) ključne dejavnike pri razlagi rezultatov. Navodila za pripravo materialov, predvsem glede zgoraj navedenih preskusov, so navedena v Dodatku A. V Dodatku B je opisanih več posebnih preskusov draženja, kadar medicinski pripomočki uporabljajo drugje kot na koži.

General Information

• Status: Withdrawn
• Publication Date: 29-Nov-2010
• Withdrawal Date: 20-Aug-2013
• ICS: 11.100 - Laboratory medicine
• ICS: 11.100.20 - Biological evaluation of medical devices
• Technical Committee: CEN/TC 206 - Biocompatibility of medical and dental materials and devices
• Drafting Committee: CEN/TC 206 - Biocompatibility of medical and dental materials and devices
• Current Stage: 9960 - Withdrawal effective - Withdrawal
• Start Date: 21-Aug-2013
• Completion Date: 21-Aug-2013
• Directive: 2007/47/EC - Directive 2007/47/EC of the European Parliament and of the council of 5 September 2007 amending Council Directive 90/385/EEC on the approximation of the laws of the Member States relating to active implantable medical devices, Council Directive 93/42/EEC concerning medical devices and Directive 98/8/EC concerning the placing of biocidal products on the market
• Directive: 90/385/EEC - Council Directive 90/385/EEC of 20 June 1990 on the approximation of the laws of the Member States relating to active implantable medical devices
• Directive: 93/42/EEC - Council Directive 93/42/EEC of 14 June 1993 concerning medical devices
• Mandate: M/BC/CEN/89/9 - Joint Standardization request to CEN/CENELEC concerning harmonized standards relating to horizontal aspects in the field of medical devices
• Ref Project: SIST EN ISO 10993-10:2010 - Biological evaluation of medical devices - Part 10: Tests for irritation and skin sensitization (ISO 10993-10:2010)

Relations

• Replaces: EN ISO 10993-10:2009 - Biological evaluation of medical devices - Part 10: Tests for irritation and delayed-type hypersensitivity (ISO 10993-10:2002, including Amd 1:2006)
• Effective Date: 04-Jul-2009
• Replaced By: EN ISO 10993-10:2013 - Biological evaluation of medical devices - Part 10: Tests for irritation and skin sensitization (ISO 10993-10:2010)
• Effective Date: 21-Aug-2013
• Replaced By: EN ISO 10993-10:2023 - Biological evaluation of medical devices - Part 10: Tests for skin sensitization (ISO 10993-10:2021)
• Effective Date: 19-Jan-2023

Standards Content (Sample)

SLOVENSKI STANDARD
SIST EN ISO 10993-10:2010
01-oktober-2010
1DGRPHãþD
SIST EN ISO 10993-10:2009
%LRORãNRRYUHGQRWHQMHPHGLFLQVNLKSULSRPRþNRYGHO3UHVNXVLGUDåHQMDLQ
SUHREþXWOMLYRVWLNRåH,62

Biological evaluation of medical devices - Part 10: Tests for irritation and skin

sensitization (ISO 10993-10:2010)

Biologische Beurteilung von Medizinprodukten - Teil 10: Prüfung auf Irritation und

Hautsensibilisierung (ISO 10993-10:2010)

Évaluation biologique des dispositifs médicaux - Partie 10: Essais d'irritation et de

sensibilisation cutanée (ISO 10993-10:2010)
Ta slovenski standard je istoveten z: EN ISO 10993-10:2010
ICS:
11.100.20 %LRORãNRRYUHGQRWHQMH Biological evaluation of
PHGLFLQVNLKSULSRPRþNRY medical devices
SIST EN ISO 10993-10:2010 en

2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

---------------------- Page: 1 ----------------------
SIST EN ISO 10993-10:2010
---------------------- Page: 2 ----------------------
SIST EN ISO 10993-10:2010
EUROPEAN STANDARD
EN ISO 10993-10
NORME EUROPÉENNE
EUROPÄISCHE NORM
August 2010
ICS 11.100.20 Supersedes EN ISO 10993-10:2009
English Version
Biological evaluation of medical devices - Part 10: Tests for
irritation and skin sensitization (ISO 10993-10:2010)

Évaluation biologique des dispositifs médicaux - Partie 10: Biologische Beurteilung von Medizinprodukten - Teil 10:

Essais d'irritation et de sensibilisation cutanée (ISO 10993- Prüfung auf Irritation und Hautsensibilisierung (ISO 10993-

10:2010) 10:2010)
This European Standard was approved by CEN on 23 July 2010.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this European

Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such national

standards may be obtained on application to the CEN Management Centre or to any CEN member.

This European Standard exists in three official versions (English, French, German). A version in any other language made by translation

under the responsibility of a CEN member into its own language and notified to the CEN Management Centre has the same status as the

official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,

Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland,

Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.

EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: Avenue Marnix 17, B-1000 Brussels

© 2010 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 10993-10:2010: E

worldwide for CEN national Members.
---------------------- Page: 3 ----------------------
SIST EN ISO 10993-10:2010
EN ISO 10993-10:2010 (E)
Contents Page

Foreword ..............................................................................................................................................................3

Annex ZA (informative) Relationship between this European Standard and the Essential

Requirements of EU Directive 93/42/EEC on Medical Devices .........................................................4

Annex ZB (informative) Relationship between this European Standard and the Essential

Requirements of EU Directive 90/385/EEC on Active Implantable Medical Devices .....................5

---------------------- Page: 4 ----------------------
SIST EN ISO 10993-10:2010
EN ISO 10993-10:2010 (E)
Foreword

This document (EN ISO 10993-10:2010) has been prepared by Technical Committee ISO/TC 194 "Biological

evaluation of medical devices" in collaboration Technical Committee CEN/TC 206 “Biological evaluation of

medical devices” the secretariat of which is held by NEN.

This European Standard shall be given the status of a national standard, either by publication of an identical

text or by endorsement, at the latest by February 2011, and conflicting national standards shall be withdrawn

at the latest by February 2011.

Attention is drawn to the possibility that some of the elements of this document may be the subject of patent

rights. CEN [and/or CENELEC] shall not be held responsible for identifying any or all such patent rights.

This document supersedes EN ISO 10993-10:2009.

This document has been prepared under a mandate given to CEN by the European Commission and the

European Free Trade Association, and supports essential requirements of EU Directives.

For relationship with EU Directives, see informative Annex ZA and ZB, which are integral parts of this

document.

According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following

countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech

Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia,

Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain,

Sweden, Switzerland and the United Kingdom.
Endorsement notice

The text of ISO 10993-10:2010 has been approved by CEN as a EN ISO 10993-10:2010 without any

modification.
---------------------- Page: 5 ----------------------
SIST EN ISO 10993-10:2010
EN ISO 10993-10:2010 (E)
Annex ZA
(informative)
Relationship between this European Standard and the Essential Requirements of EU
Directive 93/42/EEC on Medical Devices

This European Standard has been prepared under a mandate given to CEN by the European Commission

and the European Free Trade Association to provide a means of conforming to Essential Requirements of the

New Approach Directive 93/42/EEC on Medical Devices.

Once this standard is cited in the Official Journal of the European Union under that Directive and has been

implemented as a national standard in at least one Member State, compliance with the clauses of this

International Standard given in Table ZA.1 confers, within the limits of the scope of this European Standard, a

presumption of conformity with the corresponding Essential Requirements of that Directive and associated

EFTA regulations.

Table ZA.1 — Correspondence between this European Standard and Directive 93/42/EEC on medical

devices

Clause(s)/sub-clause(s) of this Essential Requirements (ERs) Qualifying remarks/Notes

European Standard of Directive 93/42/EEC

4, 5, 6, 7, 8, Annexes A, B and C 7.1, 7.2, 7.5 Within the limits of the Scope of this

standard.
6.5 and Annex C 6a Subclause 6.5 and Annex C contain
requirements that are relevant to clinical
investigations according to section 2 of
Annex X, as referred to in essential
requirement 6a of Directive 93/42/EEC.

General Note: Presumption of conformity depends on also complying with all relevant clauses/subclauses of

ISO 10993-1.

WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling

within the scope of this standard.
---------------------- Page: 6 ----------------------
SIST EN ISO 10993-10:2010
EN ISO 10993-10:2010 (E)
Annex ZB
(informative)
Relationship between this European Standard and the Essential Requirements of
EU Directive 90/385/EEC on Active Implantable Medical Devices

This European Standard has been prepared under a mandate given to CEN by the European Commission

and the European Free Trade Association to provide a means of conforming to Essential Requirements of the

New Approach Directive 90/385/EEC on active Implantable Medical Devices.

Once this Standard is cited in the Official Journal of the European Union under that Directive and has been

implemented as a national standard in at least one Member State, compliance with the clauses of this

International Standard given in Table ZB.1 confers, within the limits of the scope of this standard, a

presumption of conformity with the corresponding Essential Requirements of that Directive and associated

EFTA regulations.

Table ZB.1 — Correspondence between this European Standard and Directive 90/385/EEC on Active

Implantable Medical Devices

Clause(s)/sub-clause(s) of this Essential Requirements (ERs) Qualifying remarks/Notes

European Standard of Directive 90/385/EEC

4, 5, 6, 7, 8, Annexes A, B and C 9 (first and second indents only) Within the limits of the Scope of

this standard.
6.5 and Annex C 5a Subclause 6.5 and Annex C
contain requirements that are
relevant to clinical investigations
according to section 2 of Annex
7, as referred to in essential
requirement 5a of Directive
90/385/EEC.

General Note: Presumption of conformity depends on also complying with all relevant clauses/subclauses of

ISO 10993-1.

WARNING — Other requirements and other EU Directives may be applicable to the product(s) falling

within the scope of this standard.
---------------------- Page: 7 ----------------------
SIST EN ISO 10993-10:2010
---------------------- Page: 8 ----------------------
SIST EN ISO 10993-10:2010
INTERNATIONAL ISO
STANDARD 10993-10
Third edition
2010-08-01
Biological evaluation of medical
devices —
Part 10:
Tests for irritation and skin sensitization
Évaluation biologique des dispositifs médicaux —
Partie 10: Essais d'irritation et de sensibilisation cutanée
Reference number
ISO 10993-10:2010(E)
ISO 2010
---------------------- Page: 9 ----------------------
SIST EN ISO 10993-10:2010
ISO 10993-10:2010(E)
PDF disclaimer

This PDF file may contain embedded typefaces. In accordance with Adobe's licensing policy, this file may be printed or viewed but

shall not be edited unless the typefaces which are embedded are licensed to and installed on the computer performing the editing. In

downloading this file, parties accept therein the responsibility of not infringing Adobe's licensing policy. The ISO Central Secretariat

accepts no liability in this area.
Adobe is a trademark of Adobe Systems Incorporated.

Details of the software products used to create this PDF file can be found in the General Info relative to the file; the PDF-creation

parameters were optimized for printing. Every care has been taken to ensure that the file is suitable for use by ISO member bodies. In

the unlikely event that a problem relating to it is found, please inform the Central Secretariat at the address given below.

COPYRIGHT PROTECTED DOCUMENT
© ISO 2010

All rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized in any form or by any means,

electronic or mechanical, including photocopying and microfilm, without permission in writing from either ISO at the address below or

ISO's member body in the country of the requester.
ISO copyright office
Case postale 56 • CH-1211 Geneva 20
Tel. + 41 22 749 01 11
Fax + 41 22 749 09 47
E-mail [e-mail]
Web www.iso.org
Published in Switzerland
ii © ISO 2010 – All rights reserved
---------------------- Page: 10 ----------------------
SIST EN ISO 10993-10:2010
ISO 10993-10:2010(E)
Contents Page

Foreword ............................................................................................................................................................iv

Introduction........................................................................................................................................................vi

1 Scope......................................................................................................................................................1

2 Normative references............................................................................................................................1

3 Terms and definitions ...........................................................................................................................2

4 General principles — Step-wise approach .........................................................................................4

5 Pretest considerations..........................................................................................................................4

5.1 General ...................................................................................................................................................4

5.2 Types of material ...................................................................................................................................5

5.3 Information on chemical composition ................................................................................................5

6 Irritation tests.........................................................................................................................................6

6.1 In vitro irritation tests............................................................................................................................6

6.2 In vivo irritation tests — Factors to be considered in design and selection of in vivo tests ........6

6.3 Animal irritation test..............................................................................................................................7

6.4 Animal intracutaneous (intradermal) reactivity test ........................................................................11

6.5 Human skin irritation test ...................................................................................................................14

7 Skin sensitization tests.......................................................................................................................15

7.1 Choice of test methods.......................................................................................................................15

7.2 Murine Local Lymph Node Assay (LLNA).........................................................................................15

7.3 Guinea pig assays for the detection of skin sensitization..............................................................18

7.4 Important factors affecting the outcome of the test ........................................................................19

7.5 Guinea pig maximization test (GPMT)...............................................................................................20

7.6 Closed-patch test (Buehler test) ........................................................................................................23

8 Key factors in interpretation of test results......................................................................................26

Annex A (normative) Preparation of materials for irritation/sensitization testing.....................................27

Annex B (normative) Special irritation tests..................................................................................................29

Annex C (normative) Human skin irritation test ............................................................................................44

Annex D (informative) In vitro tests for skin irritation...................................................................................48

Annex E (informative) Method for the preparation of extracts from polymeric test materials .................54

Annex F (informative) Background information ............................................................................................57

Bibliography......................................................................................................................................................61

© ISO 2010 – All rights reserved iii
---------------------- Page: 11 ----------------------
SIST EN ISO 10993-10:2010
ISO 10993-10:2010(E)
Foreword

ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies

(ISO member bodies). The work of preparing International Standards is normally carried out through ISO

technical committees. Each member body interested in a subject for which a technical committee has been

established has the right to be represented on that committee. International organizations, governmental and

non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the

International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.

International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.

The main task of technical committees is to prepare International Standards. Draft International Standards

adopted by the technical committees are circulated to the member bodies for voting. Publication as an

International Standard requires approval by at least 75 % of the member bodies casting a vote.

Attention is drawn to the possibility that some of the elements of this document may be the subject of patent

rights. ISO shall not be held responsible for identifying any or all such patent rights.

ISO 10993-10 was prepared by Technical Committee ISO/TC 194, Biological evaluation of medical devices.

This third edition cancels and replaces the second edition (ISO 10993-10:2002), which has been technically

revised.

ISO 10993 consists of the following parts, under the general title Biological evaluation of medical devices:

⎯ Part 1: Evaluation and testing within a risk management process
⎯ Part 2: Animal welfare requirements
⎯ Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity
⎯ Part 4: Selection of tests for interactions with blood
⎯ Part 5: Tests for in vitro cytotoxicity
⎯ Part 6: Tests for local effects after implantation
⎯ Part 7: Ethylene oxide sterilization residuals

⎯ Part 9: Framework for identification and quantification of potential degradation products

⎯ Part 10: Tests for irritation and skin sensitization
⎯ Part 11: Tests for systemic toxicity
⎯ Part 12: Sample preparation and reference materials

⎯ Part 13: Identification and quantification of degradation products from polymeric medical devices

⎯ Part 14: Identification and quantification of degradation products from ceramics

⎯ Part 15: Identification and quantification of degradation products from metals and alloys

iv © ISO 2010 – All rights reserved
---------------------- Page: 12 ----------------------
SIST EN ISO 10993-10:2010
ISO 10993-10:2010(E)
⎯ Part 16: Toxicokinetic study design for degradation products and leachables
⎯ Part 17: Establishment of allowable limits for leachable substances
⎯ Part 18: Chemical characterization of materials

⎯ Part 19: Physico-chemical, morphological and topographical characterization of materials [Technical

Specification]

⎯ Part 20: Principles and methods for immunotoxicology testing of medical devices [Technical Specification]

© ISO 2010 – All rights reserved v
---------------------- Page: 13 ----------------------
SIST EN ISO 10993-10:2010
ISO 10993-10:2010(E)
Introduction

This part of ISO 10993 assesses possible contact hazards from chemicals released from medical devices,

which may produce skin and mucosal irritation, eye irritation or skin sensitization.

Some materials that are included in medical devices have been tested, and their skin or mucosal irritation or

sensitization potential has been documented. Other materials and their chemical components have not been

tested and may induce adverse effects when in contact with human tissue. The manufacturer is thus obliged

to evaluate each device for potential adverse effects prior to marketing.

Traditionally, small animal tests are performed prior to testing on humans to help predict human response.

More recently, in vitro tests as well as human tests have been added as adjuncts or alternatives. Despite

progress and considerable effort in this direction, a review of findings suggests that currently no satisfactory

in vitro test has been devised to eliminate the requirement for in vivo testing. Where appropriate, the

preliminary use of in vitro methods is encouraged for screening purposes prior to animal testing. In order to

reduce the number of animals used, this part of ISO 10993 presents a step-wise approach, with review and

analysis of test results at each stage. An animal test is usually required prior to human testing.

It is intended that these studies be conducted using Good Laboratory Practice and comply with regulations

related to animal welfare. Statistical analysis of data is recommended and should be used whenever

appropriate.

This part of ISO 10993 is intended for use by professionals, appropriately qualified by training and experience,

who are able to interpret its requirements and judge the outcomes of the evaluation for each medical device,

taking into consideration all the factors relevant to the device, its intended use and the current knowledge of

the medical device provided by review of the scientific literature and previous clinical experience.

The tests included in this part of ISO 10993 are important tools for the development of safe products, provided

that these are executed and interpreted by trained personnel.

This part of ISO 10993 is based on numerous standards and guidelines, including OECD Guidelines,

U.S. Pharmacopoeia and the European Pharmacopoeia. It is intended to be the basic document for the

selection and conduct of tests enabling evaluation of irritation and dermal sensitization responses relevant to

safety of medical materials and devices.
vi © ISO 2010 – All rights reserved
---------------------- Page: 14 ----------------------
SIST EN ISO 10993-10:2010
INTERNATIONAL STANDARD ISO 10993-10:2010(E)
Biological evaluation of medical devices —
Part 10:
Tests for irritation and skin sensitization
1 Scope

This part of ISO 10993 describes the procedure for the assessment of medical devices and their constituent

materials with regard to their potential to produce irritation and skin sensitization.

This part of ISO 10993 includes:

a) pretest considerations for irritation, including in silico and in vitro methods for dermal exposure;

b) details of in vivo (irritation and sensitization) test procedures;
c) key factors for the interpretation of the results.

Instructions are given in Annex A for the preparation of materials specifically in relation to the above tests. In

Annex B several special irritation tests are described for application of medical devices in areas other than skin.

2 Normative references

The following referenced documents are indispensable for the application of this document. For dated

references, only the edition cited applies. For undated references, the latest edition of the referenced

document (including any amendments) applies.

ISO 10993-1:2009, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk

management process

ISO 10993-2, Biological evaluation of medical devices — Part 2: Animal welfare requirements

ISO 10993-9, Biological evaluation of medical devices — Part 9: Framework for identification and

quantification of potential degradation products

ISO 10993-12, Biological evaluation of medical devices — Part 12: Sample preparation and reference materials

ISO 10993-13, Biological evaluation of medical devices — Part 13: Identification and quantification of

degradation products from polymeric medical devices

ISO 10993-14 Biological evaluation of medical devices — Part 14: Identification and quantification of

degradation products from ceramics

ISO 10993-15, Biological evaluation of medical devices — Part 15: Identification and quantification of

degradation products from metals and alloys

ISO 10993-18, Biological evaluation of medical devices — Part 18: Chemical characterization of materials

ISO 14155-1, Clinical investigation of medical devices for human subjects — Part 1: General requirements

ISO 14155-2, Clinical investigation of medical devices for human subjects — Part 2: Clinical investigation plans

© ISO 2010 – All rights reserved 1
---------------------- Page: 15 ----------------------
SIST EN ISO 10993-10:2010
ISO 10993-10:2010(E)
3 Terms and definitions

For the purposes of this document, the terms and definitions given in ISO 10993-1 and the following apply.

3.1
allergen
sensitizer

substance or material that is capable of inducing a specific hypersensitivity reaction upon repeated contact

with that substance or material
3.2
blank

extraction vehicle not containing the test material, retained in a vessel identical to that which holds the test

material and subjected to identical conditions to which the test material is subjected during its extraction

NOTE The purpose of the blank control is to evaluate possible confounding effects due to the extraction vessel,

vehicle and extraction process.
3.3
challenge
elicitation

process following the induction phase, in which the immunological effects of subsequent exposures in an

individual to the inducing material are examined
3.4
dose
dosage

amount of test sample administered (e.g. mass, volume) expressed per unit of body weight or surface area

NOTE The terms are often used interchangeably (more commonly dosage).
3.5
erythema
reddening of the skin or mucous membrane
3.6
eschar
scab or discoloured slough of skin
3.7
extract

liquid or suspension that results from exposing a test or control material to a solvent under controlled

conditions
3.8
induction

process that leads to the de novo generation of an enhanced state of immunological activity in an individual, to

a specific material
3.9
irritant
agent that produces irritation
3.10
irritation

localized non-specific inflammatory response to single, repeated or continuous application of a substance/material

NOTE Skin irritation is a reversible reaction and is mainly characterized by local erythema (redness) of the skin.

2 © ISO 2010 – All rights reserved
---------------------- Page: 16 ----------------------
SIST EN ISO 10993-10:2010
ISO 10993-10:2010(E)
3.11
necrosis

cell death as a direct result of irreversible changes caused by injury or disease

NOTE One should be aware that tissue repair will occur either resulting in complete functional restoration or resulting

in scar formation.
3.12
negative control

any well-characterized material or substance that, when tested by a specific procedure, demonstrates the

suitability of the procedure to yield a reproducible, appropriately negative, non-reactive or minimal response in

the test system

NOTE In practice, negative controls include blanks, vehicles/solvents and reference materials.

3.13
oedema
swelling due to abnormal infiltration of fluid into the tissues
3.14
positive control

any well-characterized material or substance that, when evaluated by a specific test method, demonstrates

the suitability of the test system to yield a reproducible, appropriately positive or reactive response in the test

system
3.15
skin corrosion

production of irreversible damage to the skin, manifested as visible necrosis through the epidermis and into

the dermis, following application of a test sample

EXAMPLE The action of a compound/chemical/test sample resulting in ulceration of skin (see 3.19).

3.16
skin sensitization
allergic contact dermatitis
immunologically mediated cutaneous reaction to a substance

NOTE In the human, the responses can be characterized by pruritis, erythema, oedema, papules, vesicles, bullae or

a combination of these. In other species the reactions can differ and only erythema and oedema can be seen.

3.17
test material

material, device, device portion or component thereof that is sampled for biological or chemical testing

3.18
test sample

material, device, device portion, component, extract or portion thereof that is subjected to biological or

chemical testing or evaluation
3.19
ulceration
open sore representing loss of superficial tissue
3.20
vehicle

liquid used to moisten, dilute, suspend, extract or dissolve the test substance/material

© ISO 2010 – All rights reserved 3
---------------------- Page: 17 ----------------------
SIST EN ISO 10993-10:2010
ISO 10993-10:2010(E)
4 General principles — Step-wise approach

The available methods for testing irritation and sensitization were developed specifically to detect skin and

mucous membrane irritation and skin sensitization potential. Other types of adverse effect are generally not

predicted by these tests. For medical devices that are used as implants or external communicating devices,

intradermal testing is more relevant in approaching the application and so for detection of irritation activity,

intracutaneous testing shall be used as described in 6.4.

This part of ISO 10993 requires a step-wise approach, which shall include one or more of the following:

a) characterization of test material, involving chemical characterization and analysis of the test sample

according to the general principles described in ISO 10993-9, ISO 10993-13, ISO 10993-14,

ISO 10993-15 and ISO 10993-18;

b) literature review, including an evaluation of chemical and physical properties, and information on the

irritation and sensitization potential of any product constituent as well as structurally-related chemicals

and materials;

c) in accordance with ISO 10993-2, in vitro tests in preference to in vivo tests shall be considered, and

replacement of the latter as new in vitro tests are scientifically validated and become reasonably and

practicably available. For the evaluation of skin irritation and corrosion, in vitro alternatives are available

for chemicals; there are currently no internationally validate
...