kSIST FprEN ISO 10993-7:2025

SLOVENSKI STANDARD
oSIST prEN ISO 10993-7:2024
01-september-2024
Biološko ovrednotenje medicinskih pripomočkov - 7. del: Ostanki po sterilizaciji z
etilenoksidom (ISO/DIS 10993-7:2024)
Biological evaluation of medical devices - Part 7: Ethylene oxide sterilization residuals
(ISO/DIS 10993-7:2024)
Biologische Beurteilung von Medizinprodukten - Teil 7: Ethylenoxid-
Sterilisationsrückstände (ISO/DIS 10993-7:2024)
Évaluation biologique des dispositifs médicaux - Partie 7: Résidus de stérilisation à
l'oxyde d'éthylène (ISO/DIS 10993-7:2024)
Ta slovenski standard je istoveten z: prEN ISO 10993-7
ICS:
11.100.20 Biološko ovrednotenje Biological evaluation of
medicinskih pripomočkov medical devices
oSIST prEN ISO 10993-7:2024 en,fr,de
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

oSIST prEN ISO 10993-7:2024
oSIST prEN ISO 10993-7:2024
DRAFT
International
Standard
ISO/DIS 10993-7
ISO/TC 194
Biological evaluation of medical
Secretariat: DIN
devices —
Voting begins on:
Part 7: 2024-06-17
Ethylene oxide sterilization
Voting terminates on:
2024-09-09
residuals
Évaluation biologique des dispositifs médicaux —
Partie 7: Résidus de stérilisation à l'oxyde d'éthylène
ICS: 11.100.20
THIS DOCUMENT IS A DRAFT CIRCULATED
FOR COMMENTS AND APPROVAL. IT
IS THEREFORE SUBJECT TO CHANGE
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This document is circulated as received from the committee secretariat.
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Reference number
ISO/DIS 10993-7:2024(en)
oSIST prEN ISO 10993-7:2024
DRAFT
ISO/DIS 10993-7:2024(en)
International
Standard
ISO/DIS 10993-7
ISO/TC 194
Biological evaluation of medical
Secretariat: DIN
devices —
Voting begins on:
Part 7:
Ethylene oxide sterilization
Voting terminates on:
residuals
Évaluation biologique des dispositifs médicaux —
Partie 7: Résidus de stérilisation à l'oxyde d'éthylène
ICS: 11.100.20
THIS DOCUMENT IS A DRAFT CIRCULATED
FOR COMMENTS AND APPROVAL. IT
IS THEREFORE SUBJECT TO CHANGE
AND MAY NOT BE REFERRED TO AS AN
INTERNATIONAL STANDARD UNTIL
PUBLISHED AS SUCH.
This document is circulated as received from the committee secretariat.
IN ADDITION TO THEIR EVALUATION AS
BEING ACCEPTABLE FOR INDUSTRIAL,
© ISO 2024
TECHNOLOGICAL, COMMERCIAL AND
USER PURPOSES, DRAFT INTERNATIONAL
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Published in Switzerland Reference number
ISO/DIS 10993-7:2024(en)
ii
oSIST prEN ISO 10993-7:2024
ISO/DIS 10993-7:2024(en)
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Requirements . 5
4.1 General .5
4.2 Categorization of devices .6
4.3 Allowable limits .6
4.3.1 General .6
4.3.2 Limited contact devices .7
4.3.3 Prolonged contact devices .8
4.3.4 Long-term contact devices .8
4.3.5 Special situations .9
4.3.6 Tolerable contact level .10
4.4 Determination of EO and ECH residuals .11
4.4.1 Procedure .11
4.4.2 Test method validation .11
4.4.3 Product sampling .11
4.4.4 Product extraction .11
4.4.5 Multi-device Systems . 12
5 Product release .12
5.1 General . 12
5.2 Batch release of products . . 12
5.3 Release of products at defined minimum aeration time . 12
5.4 Procedure for product release using residual dissipation curves . 13
6 Adoption of products into established aeration family . 14
7 Requalification. 14
Annex A (informative) Guidance for the application of this document for the determination of
EO and ECH residuals in medical devices .15
Annex B (informative) Factors influencing product residuals .25
Annex C (informative) Rationale for the provisions of this document .28
Annex D (informative) Establishment of allowable limits for EO .33
Annex E (informative) Establishment of allowable limits for ECH .50
Annex F (informative) Ethylene Glycol .60
Annex G (normative) Evaluation of gas chromatograms .64
Annex H (informative) Gas chromatographic determination for EO and ECH .68
Annex I (informative) Preparation of EO and ECH standards .72
Annex J (informative) Ethylene oxide and ethylene chlorohydrin residual measuring methods . 76
Annex K (informative) Examples of product release methods .84
Annex ZA (informative) Relationship between this European Standard the General Safety and
Performance Requirements of Regulation (EU) 2017/745 aimed to be covered .102
Bibliography .105

iii
oSIST prEN ISO 10993-7:2024
ISO/DIS 10993-7:2024(en)
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.
The procedures used to develop this document and those intended for its further maintenance are described
in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the different types
of ISO documents should be noted. This document was drafted in accordance with the editorial rules of the
ISO/IEC Directives, Part 2 (see www.iso.org/directives).
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. Details of any patent
rights identified during the development of the document will be in the Introduction and/or on the ISO list of
patent declarations received (see www.iso.org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation of the voluntary nature of standards, the meaning of ISO specific terms and expressions
related to conformity assessment, as well as information about ISO's adherence to the World Trade
Organization (WTO) principles in the Technical Barriers to Trade (TBT), see www.iso.org/iso/foreword.html.
This document was prepared by Technical Committee ISO/TC 194, Biological and clinical evaluation of
medical devices.
This third edition cancels and replaces the second edition (ISO 10993-7:2008, ISO 10993-7:2008/Cor 1:2009
and ISO 10993-7:2008/Amd 1:2019), which has been technically revised. This edition shall be implemented
within 3 years of publication.
The main changes compared to the previous edition are as follows:
— manufacturer to define allowable limits and extraction conditions, based on the patient population and
the duration of use;
— allow for the use of a risk assessment to establish allowable limits;
— provide additional guidance on product release;
— provide additional guidance on determining residuals and the factors that affect residual.
A list of all parts in the ISO 10993 series can be found on the ISO website.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www.iso.org/members.html.

iv
oSIST prEN ISO 10993-7:2024
ISO/DIS 10993-7:2024(en)
Introduction
Requirements for the development, validation and routine control of an ethylene oxide sterilization process
for medical devices are given in International Standards developed by ISO/TC 198. The general requirements
relating to biological evaluation and testing of medical devices, selection of tests, and the allocation of devices
to categories are dealt with in International Standards developed by ISO/TC 194. The specific requirement
for ethylene oxide and other sterilization process residuals was referred to ISO/TC 194. Other International
Standards delineate particular requirements for biological testing for specific products.
As noted in the introduction to ISO 11135:2014, when determining the suitability of ethylene oxide (EO)
for sterilization of medical devices, it is important to ensure that the levels of residual EO and ethylene
chlorohydrin (ECH) pose a minimal risk to the patient in intended product use. Therefore, it is important
that the use of alternative materials and sterilization processes are considered during product design
and development. EO is known to exhibit a number of biological effects. In the development of this
document, consideration was given to these effects, which include irritation, organ damage, mutagenicity,
carcinogenicity, and reproductive effects in humans and animals. Similar consideration was given to the
harmful effects of ECH and ethylene glycol (EG). ECH can be formed when EO comes into contact with free
chloride ions, whereas EG is a hydrolytic reaction product of EO and water. In practice, for most devices,
exposure to EO and ECH is considerably lower than the maximum allowable limits established according to
this document. No allowable limits are set for ethylene glycol because risk assessment indicated that when
EO residuals are controlled, it is unlikely that biologically significant residuals of EG would be present.
Requirements herein are in addition to the biological evaluation requirements as indicated in ISO 10993-1.
The biological evaluation, combined with the EO-sterilization process residual limits, form the justification
that an EO-sterilized device is safe for its anticipated contact duration. Maximum allowable residuals for
ECH, when ECH has been found to be present in medical devices sterilized with EO, are also specified. Local
effects (e.g., irritation) have been considered and are incorporated in the tolerable contact level (TCL) as
given in 4.3.6.2 and Annex D for EO, and in 4.3.6.3 and Annex E for ECH.
In this edition of ISO 10993-7 an uncertainty factor approach based on ISO 10993-17:2023 is used to derive
EO and ECH exposure duration-specific tolerable intake (TI) values (expressed in µg/kg/d). Unique in this
version of ISO 10993-7 is the conversion of each EO and ECH TI value into subpopulation-specific cumulative
exposure-allowable limit values (expressed in mg/device), which are used to determine the extent that
EO and ECH, extracted under clinically relevant conditions and time-periods, needs to be reduced post-
sterilization.
This edition of ISO 10993-7 applies a different approach as compared to ISO 10993-17:2023 to establishing
allowable limits to make it useful for development, validation, and routine control of ethylene oxide
sterilization in the manufacture of finished medical devices with focus on the risk assessments associated
with 3 chemical constituents that are potentially left in medical devices sterilized with ethylene oxide.
ISO 10993-7 extends this knowledge further by calculating the largest amount of EO, ECH or EG that can
be present in a medical device such that it would always meet the requirements of ISO 10993-17 when
that device has been exposed to the validated sterilization cycle parameters. This maximum amount or
allowable limit is expressed in mg/device deemed acceptable when taken into the body through exposure
to that medical device. These allowable limits will help determine the appropriate sterilization parameters
such as sterilant gas concentration and dwell, as well as aeration temperature and hold time when validating
the sterilization process to be used for a product or group of products. Further the allowable limits may be
used by regulatory bodies, manufacturers, and processors to optimize processes and aid in the selection and
qualification of alternative materials in order to protect patient health.

v
oSIST prEN ISO 10993-7:2024
oSIST prEN ISO 10993-7:2024
DRAFT International Standard ISO/DIS 10993-7:2024(en)
Biological evaluation of medical devices —
Part 7:
Ethylene oxide sterilization residuals
1 Scope
This document specifies allowable limits for residual ethylene oxide (EO) and ethylene chlorohydrin
(ECH) in EO-sterilized medical devices, procedures for the measurement of EO and ECH, and methods for
determining compliance so that devices may be released. Additional background, including guidance and a
flowchart showing how this document is applied, are also included in the informative annexes.
EO-sterilized devices or components that have neither direct nor indirect patient contact (e.g., in vitro
diagnostic devices) are out of scope of this document. This document does not apply to devices that have
been demonstrated to not absorb or retain EO or its degradation product ECH, such as medical devices made
[228]
exclusively of metal alloys and glass, see Annex C.5 .
NOTE This document does not specify limits for ethylene glycol (EG). No device limits are specified for EG because
the risk assessment in Annex F indicates that calculated allowable levels are higher than those likely to occur in a
medical device.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content constitutes
requirements 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 10993-1:2018, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
ISO 10993-23, Biological evaluation of medical devices — Part 23: Tests for irritation
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 10993-1 and the following apply.
ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/
3.1
aeration
part of the sterilization cycle during which the sterilizing agent and/or its reaction products desorb from
the health care product until predetermined levels are reached
[SOURCE: ISO 11139:2018, 3.7]
oSIST prEN ISO 10993-7:2024
ISO/DIS 10993-7:2024(en)
3.2
allowable limit
AL
amount of residual EO or ECH on a single device that is without appreciable harm to health (3.10) for the
patient’s whole exposure to the device
Note 1 to entry: Allowable limits are expressed in mg/device for each applicable exposure period. These limits
represent acceptable biological risks for medical devices under the circumstances of their anticipated contact duration.
3.3
cumulative exposure
total quantity of EO and ECH that contacts the body for a specified period of time
Note 1 to entry: Cumulative exposure applies when multiple uses of the same device for same patient or user applies.
For example, when more than one device is used simultaneously or repeatedly over a specified period of time.
Note 2 to entry: If a device usage period is less than limited or prolonged contact exposure category, but intended for
repeated or multiple usages that exceed another exposure (prolonged or long-term) category, the total residuals are
combined and the additional categories apply, e.g., dialyzer cartridges used for less than 24 hours, but repeatedly used
long-term.
3.4
concomitant exposure factor
CEF
numerical safety factor that accounts for patient exposure to the simultaneous use of other EO sterilized
medical devices different from the subject medical device
Note 1 to entry: CEF is calculated from the reciprocal of the number of devices (1/device) used during a procedure.
The default value of 0,2 assumes five other devices are used during a procedure, see Clause 4.4.5. Annex A.2.4 and
Annex D.3.2 for further details.
3.5
cycle
set of parameters that make up the sterilization process
3.6
default value
value or factor used in the derivation of a tolerable contact level (3.24) or tolerable intake (3.26), in the
absence of specific data [e.g., an uncertainty factor (3.28)]
[SOURCE: ISO 10993-17:2023, 3.5, modified to remove worst case exposure dose and replace with tolerable
contact level]
3.7
dose-response
relationship of dosage to observable harm
Note 1 to entry: In general, there are two types of dose-response relationships. The first type is the change in response for
an individual to a range of doses. The second type is the distribution of a response among individuals to a range of doses.
[SOURCE: ISO 10993-17:2023, 3.6]
3.8
exhaustive extraction
multi-step extraction conducted until the amount of material extracted in a subsequent extraction step is
less than 10 % of that determined in the initial extraction step
Note 1 to entry: Based upon the boiling point of EO (10,7 °C) and the knowledge that substances, other than EO and
ECH, may be extracted from the device under evaluation, gravimetric analysis may not be appropriate for determining
the exhaustivity level.
[SOURCE: ISO 10993-18:2020, 3.15, modified – removal of gravimetric analysis and addition of Note 1 to entry]

oSIST prEN ISO 10993-7:2024
ISO/DIS 10993-7:2024(en)
3.9
externally communicating medical device
medical device or medical device component that is partially or wholly located outside the body but has
either direct or indirect contact with the internal body fluids and/or tissues
[SOURCE: ISO 10993-1:2018, 3.7]
3.10
harm to health
adverse reaction, such as altered morphology, physiology, growth, development, reproduction or lifespan that
a) impairs function of an organ or system, organism, or (sub)population,
b) reduces capacity to tolerate impaired function, or
c) increases susceptibility to other influences that impair function
Note 1 to entry: Examples of (sub) population include, but are not limited to: male, female, preterm neonates, adults.
[SOURCE: ISO 10993-17:2023, 3.8]
3.11
load
product, equipment, or materials to be processed together within an operating cycle
Note 1 to entry: Frequently referred to as a sterilization batch or sterilization load.
[SOURCE: ISO 11139:2018, 3.155]
3.12
implant
medical device which is intended to be totally introduced into the human body or to replace an epithelial
surface or the surface of the eye by means of clinical intervention and which is intended to remain in place
after the procedure
[SOURCE: ISO 10993-1:2018, 3.10]
3.13
irritation
localized non-specific inflammatory response to single, repeated, or continuous application of a substance/
material
[SOURCE: ISO 10993-17:2023, 3.12]
3.14
lowest observed adverse effect level
LOAEL
lowest concentration or amount of an identified constituent found by experiment or observation which
causes detectable harm to health (3.10) to the target organism under defined conditions of exposure
[SOURCE: ISO 10993-17:2023, 3.13, modified – Note 1 to entry deleted.]
3.15
minimally irritating level
MIL
lowest amount per surface area of an identified constituent that is irritating to the tissue at the contact site
as determined by valid experimental or observational evidence
Note 1 to entry: Minimally irritating level is normally expressed as microgram per centimetre squared (μg/cm ).
[SOURCE: ISO 10993-17:2023, 3.15]

oSIST prEN ISO 10993-7:2024
ISO/DIS 10993-7:2024(en)
3.16
modifying factor
MF
mathematical product of uncertainty factors (3.28)
[SOURCE: ISO 10993-17:2023, 3.16]
3.17
non-irritating level
NIL
greatest amount per surface area of an identified constituent that does not elicit irritation (3.13) to the tissue
at the contact site as determined by valid experimental or observational evidence
Note 1 to entry: non-irritating level is normally expressed as microgram per centimetre squared (μg/cm ).
[SOURCE: ISO 10993-17:2023, 3.17]
3.18
no observed adverse effect level
NOAEL
greatest concentration or amount of an identified constituent found by experiment or observation which
causes no detectable harm to health (3.10) to the target organism under defined conditions of exposure
Note 1 to entry: No observed adverse effect level is normally expressed as microgram per kilogram of body weight per
day (μg/kg/d).
[SOURCE: ISO 10993-17:2023, 3.18]
3.19
physiologically based pharmacokinetic (PBPK) modelling
system of modelling biological effects taking into account metabolic and pharmacokinetic differences among
species of animals
Note 1 to entry: Such data should be utilized whenever available and applicable to medical device anticipated contact
duration.
3.20
Residual
quantity of EO or ECH that remains in or on the product after EO sterilization
3.21
safety
freedom from unacceptable risk
[SOURCE: ISO 14971:2019, 3.26]
3.22
simulated-use extraction
extraction using a method that simulates clinical use
Note 1 to entry: A simulated-use extraction is performed to estimate the type and amount of substances that are
expected to be released from a medical device during its clinical use. A simulated-use extraction is designed to
produce an extractables profile that represents the worst-case leachables profile, meaning that all leachables are also
extractables and the levels of all individual extractables are at least equal to the level of all individual leachables.
[SOURCE: ISO 10993-18:2020, 3.35]
3.23
surface contacting medical device
device that contacts intact skin, mucosal membrane or breached or compromised surfaces

oSIST prEN ISO 10993-7:2024
ISO/DIS 10993-7:2024(en)
3.24
tolerable contact level
TCL
estimate of the surface-contact exposure to an identified constituent that is without appreciable irritation (3.13)
Note 1 to entry: Tolerable contact level is normally expressed as microgram per centimetre squared (μg/cm ) of tissue
at the contact site.
[SOURCE: ISO 10993-17:2023, 3.25]
3.25
tolerable exposure
TE
product of the tolerable intake (3.26), the body mass, and the concomitant exposure factor
Note 1 to entry: It is normally expressed in milligrams per day to the patient.
3.26
tolerable intake
TI
estimate of the daily exposure of an identified constituent over a specified time period (e.g., acute, subacute,
sub-chronic, or chronic), on the basis of body weight, that is considered to be without appreciable harm to
health (3.10)
Note 1 to entry: Tolerable intake is normally expressed as microgram per kilogram of body weight per day (μg/kg/d).
It is derived to establish an allowable limit for a medical device constituent.
[SOURCE: ISO 10993-17:2023, 3.26]
3.27
toxicological risk assessment
determination of whether an exposure dose to a constituent can or cannot elicit appreciable harm to health (3.10)
[SOURCE: ISO 10993-17:2023, 3.29]
3.28
uncertainty factor
UF
numerical values that account for uncertainties when extrapolating a point of departure to individuals who
can be exposed to a constituent of toxicological concern
EXAMPLE Examples of extrapolation types include, but are not limited to: intraspecies, interspecies, dose route
and study duration.
[SOURCE: ISO 10993-17:2023, 3.31]
4 Requirements
4.1 General
This clause specifies maximum allowable residuals for ethylene oxide (EO) and ethylene chlorohydrin
(ECH) for each individual medical device sterilized with EO. Local (acute) effects (e.g., irritation) have been
considered and are incorporated in the tolerable contact level (TCL).
The requirements in this document are in addition to the requirements set out in ISO 10993-1. All applicable
requirements of ISO 10993-1 shall take into account the EO residual level at the time of release for each
individually designed medical device. Results of the biological assessment of the device might lead to other
limits than those specified in 4.3, which are designed to protect against local irritation and systemic effects.
This document shall not be used for commercially marketed medical devices to mandate a reassessment
of historical residuals data assessed previously using the appropriate edition of this document at the time

oSIST prEN ISO 10993-7:2024
ISO/DIS 10993-7:2024(en)
of the assessment. This includes confirmation that none of the issues identified in ISO 10993-1:2018, 4.9
have occurred; otherwise, a new assessment to demonstrate compliance to allowable limits is needed. This
assessment may also include re-testing.
NOTE 1 The previous versions of this standard reported a limit of 4 mg for EO and 9 mg for ECH for adults with
limited contact (with CEF = 0,2) for 70 kg adult population and a UF1 of 10 for intra-species variability. From a
toxicological point of view these values are not significantly different from the values calculated in the current revision
of this standard and thus, these changes in allowable limits do not warrant re-evaluating product that met the limits of
the previous version of this standard.
A flowchart providing guidance for the application of this document to the determination of EO residuals in
medical devices is presented in Annex A.
NOTE 2 Information on the derivation of the limits in this document as well as other background information and
guidance relevant to the use of this document is contained in the informative annexes.
4.2 Categorization of devices
In establishing the maximum daily doses of EO and ECH that a medical device is allowed to deliver to
patients, the medical device shall be categorized according to the duration of body contact in accordance
with ISO 10993-1:
a) Limited contact – medical devices whose cumulative sum of single, multiple, or repeated duration of
contact is up to 24 h.
b) Prolonged contact – medical devices whose cumulative sum of multiple, or repeated contact time is
likely to exceed 24 h but not exceed 30 d.
c) Long-term contact – medical devices whose cumulative sum of multiple, or repeated contact time
exceeds 30 d.
If a material or device can be placed in more than one duration category, the more rigorous testing and/or
evaluation considerations shall apply. With multiple exposures, the decision into which category a device is
placed shall take into account the potential cumulative effect, bearing in mind the period of time over which
these exposures occur.
EO or ECH testing is not required for devices with transitory body contact in line with ISO 10993-1:2018,
5.3.2. However, for products made with materials that could be left in contact with body, such as coatings
or lubricants, after the device is removed, a more detailed biocompatibility assessment can be necessary.
Cumulative use should also be considered.
4.3 Allowable limits
4.3.1 General
For each medical device, the maximum exposure of EO and ECH to patients shall not exceed the allowable
limit (see Table 1) for any of the applicable exposure categories (see 4.2). Alternative limits may be calculated
based on risk assessment that accounts for device usage and patient population. The procedure that was
used to establish the tolerable intake (TI) is described in Annex D for EO, in Annex E for ECH.
Prolonged contact devices carry additional limits for the first 24 h exposure period and, in the case of the
long-term contact devices, for the first 24 h period and the first 30 d period. These limits place constraints
on the amount of EO and ECH that can be delivered to the patient during these early time periods.
The concomitant exposure factor (CEF) uses a default value of 0,2 based on 5 devices used simultaneously. If
data are available on the number of devices used at one time, e.g., in multi-device systems, convenience kits,
long-term contact devices, then the default CEF of 0,2 may be modified (see 4.4.5, A.2.4 and D.3.2 for further
justification).
oSIST prEN ISO 10993-7:2024
ISO/DIS 10993-7:2024(en)
The Tolerable Exposure (TE) shall be calculated based on the tolerable intake (TI) multiplied by body mass
(m ) and CEF.
b
TE=×TI m ×CEF (1)
b
The allowable limit shall be determined based on tolerable exposure multiplied by the days in the category
unless an alternative limit can be justified.
numberofdaysof themedicaldevicecontactduration 
AL=×TE (2)
 
numberoffdevicesusedduringthisduration
 
The intended population shall be documented.
NOTE Cumulative limits (total quantity per period of use) are protective for inhalation and parenteral routes of
exposure because the lowest point of departure (POD) is selected, which is protective of these exposure routes.
Table 1 — Default values for formulae (1) and (2)
TI for EO TI for ECH CEF Anticipated contact duration
Contact Category
mg/kg/d mg/kg/d default d
Limited 0,3 0,64 1
Prolonged 0,3 0,27 No more than 30
0,2
Default 25 000 d
Long-term 0,02 0,029 No more than [5 840 d (0 to 16 years)]
Default [19 160 d (> 16 years)]
4.3.2 Limited contact devices
The allowable limits (AL) for limited contact devices are based on the tolerable intake (TI) value of 0,3 mg/
kg/d for EO, 0,64 mg/kg/d for ECH, with CEF = 0,2 (default) as established in clause D.3 and clause E.4
respectively. The total EO and ECH cumulative exposure estimate obtained by simulated-use or exhaustive
extraction shall be compared to the limited contact allowable limit, unless otherwise justified. Alternatively,
an assessment targeted to evaluate toxicological risk associated with exposure to EO or ECH from the
anticipated contact duration of a specific device can be used to determine the appropriate limits.
TE=×TI m ×CEF (3)
b
 
ALforEOm=×03,/gkgd/,m ××02 (4)
b  
numberofdevicesusedduringthisdurration
 
 1 
ALforECH=×06,/40mg kg/,d m ××2 (5)
b  
numberofdevicesusedduringthisdduration
 
Examples of allowable limits in Table 2 are based on selected patient populations. Based on the device usage
and intended patient population(s), other allowable limits may be more appropriate.
Table 2 — Examples of limited contact allowable limits
Patient Weight EO ECH
Patient Population
kg mg/device mg/device
Adult – Unisex (> 16 years) 60 3,6 mg/device 7,7 mg/device
Adolescent (10 to 16 years) 25 1,5 mg/device 3,2 mg/device
Child (1 to 9 years) 10 0,6 mg/device 1,3 mg/device
Infant (< 1 year) 3,5 0,21 mg/device 0,45 mg/device
NOTE The lowest patient population weight, based on the anticipated contact duration for the device, should be used, see C.4.

oSIST prEN ISO 10993-7:2024
ISO/DIS 10993-7:2024(en)
4.3.3 Prolonged contact devices
The allowable limits for prolonged contact devices are based on TI value of 0,3 mg/kg/d for EO, 0,27 mg/kg/d
for ECH, body mass m , and with CEF = 0,2 (default) as established in clause D.3 and clause E.4. The cumulative
b
exposure estimate obtained by simulated use extraction or exhaustive extraction shall be compared to the
applicable prolonged duration limit for up to 30 d, unless otherwise justified. Cumulative allowable limits in
Table 3 are based on a CEF of 0,2 and 10 d of anticipated contact. Alternatively, an assessment targeted to
evaluate toxicological risk associated with exposure to EO or ECH from the anticipated contact of a specific
device can be used to determine the appropriate limits.
numberof daysof themedicaldevicecontactduration
 
AL=×TI m ××CEF (6)
b
 
nnumberof devicesusedduringthisduration
 
numberofdaysof themedicaldeviceconntactduration
 
ALforEOm=×03,/gkgd/,m ××02
b  
numberofdevicesusedduringthisduration
(7)
 
upptod30
numberofdaysof themedicaldeviceccontactduration 
ALforECH=×02,/70mg kg/,d m ××2
b  
numberofdevicesusedduringthisduration
(8)
 
upto30d
Prolonged-contact devices shall meet Limited Contact allowable limits in 4.3.2 during the first 24 h period.
Table 3 — Examples of prolonged contact allowable Limits for 10 d anticipated contact
Patient Weight EO ECH
Patient Population
kg mg/device mg/device
Adult – Unisex (> 16 years) 60 36 32
Adolescent (10 to 16 years) 25 15 14
Child (1 to 9 years) 10 6,0 5,4
Infant (< 1 year) 3,5 2,1 1,9
NOTE The lowest patient population weight, based on the anticipated contact duration for the device, should be used, see C.4.
4.3.4 Long-term contact devices
4.3.4.1 Ethylene oxide
For EO, the tolerable exposure for long-term use devices is based on TI value of 0,02 mg/kg/d. The allowable
limit is determined by multiplying the TE with the number of days of anticipated contact from a single or
repeated use of a device for general populations (adults).
AdultTET=×ICm ×=EF 00,,26××00kg 20= ,/24mg d (9)
EO b
numberof daysof themedicaldevicecontactdurration
 
AdultALm=×02,/4 gd (10)
EO  
numberof devicesusedduringthisduration
 
For devices to be used for paediatric patients during a specific time frame (age), the TE value can be
calculated based upon the values given in Table D.9. For a device intended to be used throughout paediatric
time frame (age 0 to 16 y) and through adulthood, the TE value is 0,11 mg/d, see D.5.7. The cumulative
exposure estimate should be compared to the applicable allowable limit, unless otherwise justified.
Paediatric TE = TI × m × CEF (11)
EO b
oSIST prEN ISO 10993-7:2024
ISO/DIS 10993-7:2024(en)
numberofdaysof themedicaldevicecontactduraation 
PaediatricAL =×TE (12)
EO  
numberofdevicesusedduringthisduration
 
Long-term contact devices shall also meet limited and prolonged allowable limits in 4.3.2 and 4.3.3 during
the first 24 h period and the first 30 d, respectively.
4.3.4.2 Ethylene chlorohydrin
For ECH, the tolerable exposure for long-term use devices is based on TI value of 0,029 mg/kg/d. The
allowable limit is determined by multiplying the TE with the number of days of anticipated contact from a
single or repeated use of a device for general populations (adults) based on the anticipated contact duration.
Adult TE = 0,029 mg/kg/d × 60 kg × 0,2 = 0,35 mg/d (13)
ECH
numberofdaysof themedicaldevicecontaactduration
 
AdultALT= Em03,/5 gd × (14)
()
ECH  
numberofdevicesusedduringthisduration
 
For devices to be used for paediatric patients during a specific time frame, the TE value can be calculated
based upon the values given in Table E.5. For a device intended to be used for throughout the paediatric
time frame (age 0 to 16 years) and through adulthood the TE value is 0,16 mg/d, see E.4.2.3. The cumulative
exposure estimate should be compared to the applicable allowable limit, unless otherwise justified.
Paediatric TE = TI (0,029 mg/kg/d) × m × CEF (15)
ECH b
numberofdaysof themedicaldevicecontactdurration
 
PaediatricAL =×TE (16)
ECH  
numberofdevicesusedduringthisduration
 
Long-term contact devices shall also meet limited and prolonged allowable limits in 4.3.2 and 4.3.3 during
the first 24 h period and the first 30 d, respectively.
4.3.5 Special situations
4.3.5.1 General
For certain medical devices, the default allowable limits for EO and ECH are not appropriate. The rationale for
special situation EO and ECH limits that are at variance with the general requirements are in Annex C. When
special situations apply to sensitive special populations, the limits presented in 4.3.5.1 through 4.3.5.7 shall
be adjusted, see clause C.4. Examples of limits for sensitive populations are provided in Table 4 — below.
4.3.5.2 Residue of EO in intraocular lenses shall not exceed 0,5 μg EO per lens per day, or 1,25 μg per
lens. Prorate limits for other intraocular devices are set on the basis of the mass of the device, with the
mass of an intraocular lens taken as 20 mg. The acceptability of ECH levels in intraocular devices made from
viscoelastic materials that contain chlorine may need to be evaluated, as the level of ECH that results in
ocular toxicity is about four times greater than the corresponding EO level.
4.3.5.3 For blood cell separators used in patient and donor blood collection, the limited contact limit for
adults is 9 mg EO and 19 mg ECH. Prolonged and long-term EO and ECH limits apply, see 4.3.3 and 4.3.4.
4.3.5.4 For extracorporeal blood purification devices, the limited contact EO and ECH limits are 4,6 mg/
device. The EO and ECH limits for prolonged and long-term may be exceeded, see 4.3.3 and 4.3.4.
4.3.5.5 For peri
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