FprEN ISO 19238
(Main)Radiological protection - Performance criteria for service laboratories performing biological dosimetry by cytogenetics - The dicentric assay (ISO/DIS 19238:2022)
Radiological protection - Performance criteria for service laboratories performing biological dosimetry by cytogenetics - The dicentric assay (ISO/DIS 19238:2022)
This document provides criteria for quality assurance and quality control, evaluation of the performance and the accreditation of biological dosimetry by cytogenetic service laboratories using the dicentric assay performed with manual scoring.
This document is applicable to
a) the confidentiality of personal information, for the requestor and the service laboratory,
b) the laboratory safety requirements,
c) the calibration sources and calibration dose ranges useful for establishing the reference dose-response curves that contribute to the dose estimation from unstable chromosome aberration frequency and the detection limit,
d) the scoring procedure for unstable chromosome aberrations used for biological dosimetry,
e) the criteria for converting a measured aberration frequency into an estimate of absorbed dose,
f) the reporting of results,
g) the quality assurance and quality control, and
h) informative annexes containing sample instructions for requestor (see Annex A), sample questionnaire (see Annex B), sample report (see Annex C), fitting of the low dose-response curve by the method of maximum likelihood and calculating the error of the dose estimate (see Annex D), odds ratio method for cases of suspected exposure to a low dose (see Annex E), a method for determining the decision threshold and detection limit (see Annex F) and sample data sheet for recording aberrations (see Annex G).
Strahlenschutz - Durchführungskriterien für Dienstleistungslaboratorien zur Anwendung der biologischen Dosimetrie mittels zytogenetischer Verfahren - Dizentrische Chromosomenanalyse (ISO/FDIS 19238:2023)
Dieses Dokument stellt Kriterien für die Qualitätssicherung und Qualitätskontrolle, Validierung der Durchführung und Akkreditierung der biologischen Dosimetrie durch zytogenetische Dienstleistungslaboratorien, die die dizentrische Chromosomenanalyse mit manueller Auswertung verwenden, bereit.
Dieses Dokument behandelt Folgendes
a) die Vertraulichkeit von persönlichen Angaben, in Bezug auf den Auftraggeber und das Dienstleistungslaboratorium,
b) die Laboratorium-Sicherheitsanforderungen,
c) die sinnvollen Kalibrierquellen (Kalibrierstrahler) und Kalibrierdosisbereiche zur Erstellung der Referenz-Dosis-Wirkungs-Kurven, die zur Dosisabschätzung anhand der Häufigkeit von instabilen Chromosomenaberrationen beitragen, und der Nachweisgrenzen,
d) das Auswerteverfahren für instabile Chromosomenaberrationen, die für die biologische Dosimetrie verwendet werden,
e) die Kriterien für die Abschätzung der absorbierten Dosis, anhand der Häufigkeit von beobachteten Aberrationen,
f) die Berichterstattung der Ergebnisse,
g) die Qualitätssicherung und Qualitätskontrolle, und
h) informative Anhänge mit Musteranweisungen für Auftraggeber (siehe Anhang A), Musterfragebogen (siehe Anhang B), Musterbericht (siehe Anhang C), Anpassung der Niedrigdosis-Wirkungs-Kurve nach dem Maximum-Likelihood-Verfahren und Berechnung des Fehlers der Dosisschätzung (siehe Anhang D), Odds Ratio-Verfahren für Fälle einer vermuteten Exposition mit geringer Dosis (siehe Anhang E), sowie ein Verfahren zur Bestimmung der Erkennungsgrenze und Nachweisgrenze (siehe Anhang F) und ein Musterdatenblatt für die Erfassung der Aberrationen (siehe Anhang G).
Radioprotection - Critères de performance pour les laboratoires de service pratiquant la dosimétrie biologique par cytogénétique (ISO/DIS 19238:2022)
Le présent document fournit des critères pour l’assurance qualité et le contrôle qualité, l’évaluation des performances et l’accréditation des laboratoires de service pratiquant la dosimétrie biologique par cytogénétique via un dénombrement manuel des dicentriques.
Le présent document s'applique à
a) la confidentialité des informations personnelles pour le demandeur et le laboratoire de service,
b) les exigences de sécurité du laboratoire,
c) les sources d’étalonnage et les gammes de doses d’étalonnage utiles pour établir les courbes dose-réponse de référence qui contribuent à l’estimation de dose à partir de la fréquence des aberrations chromosomiques instables, et la limite de détection,
d) la procédure de dénombrement des aberrations chromosomiques instables utilisées pour la dosimétrie biologique,
e) les critères pour convertir une fréquence mesurée d’aberrations en une estimation de dose absorbée,
f) la présentation des résultats,
g) l’assurance qualité et le contrôle qualité, et
h) les annexes informatives contenant des exemples: d’instructions pour le demandeur (voir Annexe A), de questionnaire (voir Annexe B), de rapport (voir Annexe C), d’ajustement de la courbe dose-réponse aux faibles doses par la méthode du maximum de vraisemblance et en tenant compte de l’erreur de l’estimation de dose (voir Annexe D), de méthode de rapport de chances pour les cas d’exposition suspectée à une faible dose(voir Annexe E), de méthode de détermination du seuil de décision et de la limite de détection (voir Annexe F) et de tableau type pour le dénombrement des aberrations chromosomiques (voir Annexe G).
Radiološka zaščita - Merila za delovanje laboratorijev, ki izvajajo biološko dozimetrijo s citogenetiko - Diecentrična analiza (ISO/DIS 19238:2022)
General Information
Relations
Standards Content (Sample)
SLOVENSKI STANDARD
oSIST prEN ISO 19238:2022
01-november-2022
Radiološka zaščita - Merila za delovanje laboratorijev, ki izvajajo biološko
dozimetrijo s citogenetiko - Diecentrična analiza (ISO/DIS 19238:2022)
Radiological protection - Performance criteria for service laboratories performing
biological dosimetry by cytogenetics - The dicentric assay (ISO/DIS 19238:2022)
Strahlenschutz - Durchführungskriterien für Dienstleistungslaboratorien zur Anwendung
der biologischen Dosimetrie mittels zytogenetischer Verfahren - Dizentrischer Test
(ISO/DIS 19238:2022)
Radioprotection - Critères de performance pour les laboratoires de service pratiquant la
dosimétrie biologique par cytogénétique (ISO/DIS 19238:2022)
Ta slovenski standard je istoveten z: prEN ISO 19238
ICS:
13.280 Varstvo pred sevanjem Radiation protection
17.240 Merjenje sevanja Radiation measurements
oSIST prEN ISO 19238:2022 en,fr,de
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.
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oSIST prEN ISO 19238:2022
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oSIST prEN ISO 19238:2022
DRAFT INTERNATIONAL STANDARD
ISO/DIS 19238
ISO/TC 85/SC 2 Secretariat: AFNOR
Voting begins on: Voting terminates on:
2022-08-31 2022-11-23
Radiological protection — Performance criteria for
service laboratories performing biological dosimetry by
cytogenetics - The dicentric assay
ICS: 17.240; 13.280
THIS DOCUMENT IS A DRAFT CIRCULATED
FOR COMMENT AND APPROVAL. IT IS
THEREFORE SUBJECT TO CHANGE AND MAY
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oSIST prEN ISO 19238:2022
ISO/DIS 19238:2022(E)
DRAFT INTERNATIONAL STANDARD
ISO/DIS 19238
ISO/TC 85/SC 2 Secretariat: AFNOR
Voting begins on: Voting terminates on:
Radiological protection — Performance criteria for
service laboratories performing biological dosimetry by
cytogenetics - The dicentric assay
ICS: 17.240; 13.280
COPYRIGHT PROTECTED DOCUMENT
THIS DOCUMENT IS A DRAFT CIRCULATED
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© ISO 2022
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NATIONAL REGULATIONS.
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ii
© ISO 2022 – All rights reserved
PROVIDE SUPPORTING DOCUMENTATION. © ISO 2022
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oSIST prEN ISO 19238:2022
ISO/DIS 19238:2022(E)
Contents Page
Foreword .v
Introduction . vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Abbreviated terms . 3
5 Dicentric assay . 4
6 Responsibility of the requestor . 4
7 Responsibility of the service laboratory . 5
7.1 Setup and sustainment of the QA program . 5
7.2 Responsibility during service . 5
8 Confidentiality of personal information . 6
8.1 Overview . 6
8.2 Applications of the principle of confidentiality . 6
8.2.1 Delegation of responsibilities within the laboratory. 6
8.2.2 Requests for analysis . . 7
8.2.3 Transmission of confidential information . 7
8.2.4 Anonymity of samples . 7
8.2.5 Reporting of results . 7
8.2.6 Storage . 7
8.2.7 Data Security Plan . 7
9 Laboratory safety requirements . 7
9.1 Overview . 7
9.2 Microbiological safety requirements . 8
9.3 Chemical safety . 8
9.4 Optical safety requirements . 9
9.5 Safety plan . 9
10 Sample processing. 9
10.1 Culturing . 9
10.2 Scoring . 10
10.2.1 Coding of samples and slides . 10
10.2.2 Scoring techniques . 10
10.2.3 Procedure for scoring first-division metaphases . 10
10.2.4 Laboratory scoring expertise . 11
11 Calibration Curves .11
11.1 Calibration source(s) . 11
11.2 Establishment of calibration curve(s) . 11
12 Criteria for converting a measured aberration frequency into an estimate of
absorbed dose .13
12.1 General .13
12.2 Testing the distribution of aberrations per cell . 13
12.3 Comparison with the background level: Characterisation of the minimum
detectable dose. 14
12.4 Confidence limits on the number of dicentrics . 16
12.5 Calculation of absorbed dose for whole-body exposures . 17
12.6 Calculation of uncertainty on absorbed dose . 17
12.7 Acute and non-acute exposure cases . 18
12.8 Partial body and prior exposure cases . 18
12.9 Other exposure scenarios . 20
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oSIST prEN ISO 19238:2022
ISO/DIS 19238:2022(E)
13 Reporting of results .20
13.1 General . 20
13.2 Content of the report (see Annex C for a standard form) . 20
13.3 Interpretation of the results. 20
14 Quality assurance and quality control .21
14.1 Overview . 21
14.2 Specific requirements . 21
14.2.1 General . 21
14.2.2 Performance checks by laboratory inter-comparisons . 21
14.2.3 Periodical performance check of scorer qualification .22
14.2.4 Performance checks of sample transport integrity .22
14.2.5 Performance checks of sample integrity by service laboratory .23
14.2.6 Performance checks for instrumentation . 23
14.2.7 Performance checks of sample protocol . 23
14.2.8 Performance checks of sample scoring . 23
14.2.9 Performance checks of dose and confidence limits estimation .23
14.2.10 Performance checks for result report generation .23
Annex A (informative) Sample instructions for requestor .25
Annex B (informative) Sample questionnaire .27
Annex C (informative) Sample of report .29
Annex D (informative) Fitting of the low-LET dose-response curve by the method of
maximum likelihood and calculating the error of dose estimate .31
Annex E (informative) Odds ratio method for cases of suspected exposure to a low dose .34
Annex F (informative) Decision threshold and detection limit .36
Annex G Sample data sheet for recording aberrations .39
Bibliography .40
iv
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oSIST prEN ISO 19238:2022
ISO/DIS 19238:2022(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.
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 on 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 the following
URL: www.iso.org/iso/foreword.html.
This document was prepared by Technical Committee ISO/TC 85, Nuclear energy, nuclear technologies,
and radiological protection, Subcommittee SC 2, Radiological protection.
This second edition cancels and replaces the first edition (ISO 19238:2004), of which it constitutes a
minor revision.
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oSIST prEN ISO 19238:2022
ISO/DIS 19238:2022(E)
Introduction
The widening use of ionising radiations for medical, industrial, agricultural, research, and military
purposes increases the risk of overexposure of radiation workers and individuals of the general
population. Biological dosimetry, based on the study of chromosomal aberrations, mainly through the
dicentric assay, has become a routine component of accidental dose assessment. Experience with its
application in hundreds of cases of suspected or verified overexposures has proved the value of this
method and also defined its limitations. It should be emphasized that dicentric chromosome analysis is
used as a dosimeter and provides one input into the compendium of information needed for assessment
of a radiological incident.
Many studies on animals and humans have shown that one can establish a good correlation between
the results obtained in vivo and in vitro, so that in vitro established dose-effect relationships from
irradiated blood samples can be used to form calibration curves. The dicentric yield is dependent on
radiation quality and dose rate, as well as the circumstances of exposure (e.g. time since exposure,
homogeneity), so information about these variables is important for each investigation. If known, these
exposure characteristics are important for refining the aberration dose estimates. The specificity
of this technique is enhanced by the fact that generally 1 dicentric is observed per 1 000 metaphase
spreads in the normal population, and that this frequency is essentially independent of age and sex.
The precision of the technique thus depends on the number of cells observed, the background level, and
the calibration curve used. Theoretically, it is possible to detect exposure as low as 0,01 Gy, however,
for such low doses, it is necessary to analyse tens of thousands of metaphase spreads. In practice, this
level of detection is neither feasible nor necessary. The upper dose detection limits extend well into the
range of doses that are lethal to humans.
The primary purpose of this document is to provide a guideline to all laboratories in order to
perform the dicentric assay using documented and validated procedures. Secondly, it facilitates the
comparison of results obtained in different laboratories, particularly for international collaborations or
interlaboratory comparisons. Finally, laboratories newly commissioned to carry out the dicentric assay
should conform to this document in order to perform the assay reproducibly and accurately.
This document is written in the form of procedures to be adopted for biological dosimetry for
overexposures involving, at most, a few casualties. The criteria required for such measurements usually
depends upon the application of the results: radiation protection management, medical management
when appropriate, record keeping, and legal requirements. In the special situation of a mass radiation
casualty and limited resources, the technique can be applied for emergency triage analysis as described
in ISO 21243.
A part of the information in this document can be found in other international guidelines and scientific
publications, primarily in the International Atomic Energy Agency’s (IAEA) Technical Reports Series
on Biological Dosimetry. However, this document expands and standardizes the quality assurance
and quality control, the criteria of accreditation, and the evaluation of performance. This document
is generally compliant with ISO/IEC 17025, with particular consideration given to the specific needs
of biological dosimetry. The expression of uncertainties in dose estimations given in this document
comply with the ISO guide to the expression of uncertainty in measurement (ISO/IEC Guide 98-1) and
the ISO 5725 on accuracy (trueness and precision) of measurement methods and results.
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oSIST prEN ISO 19238:2022
DRAFT INTERNATIONAL STANDARD ISO/DIS 19238:2022(E)
Radiological protection — Performance criteria for
service laboratories performing biological dosimetry by
cytogenetics - The dicentric assay
1 Scope
This document provides criteria for quality assurance and quality control, evaluation of the
performance, and the accreditation of biological dosimetry by cytogenetic service laboratories using
the dicentric assay performed with manual scoring.
This document addresses
a) the confidentiality of personal information, for the requestor and the service laboratory,
b) the laboratory safety requirements,
c) the calibration sources and calibration dose ranges useful for establishing the reference dose-effect
curves that contribute to the dose estimation from unstable chromosome aberration frequency and
the detection limit,
d) the scoring procedure for unstable chromosome aberrations used for biological dosimetry,
e) the criteria for converting a measured aberration frequency into an estimate of absorbed dose,
f) the reporting of results,
g) the quality assurance and quality control,
h) informative annexes containing sample instructions for requestor, sample questionnaire, sample
report, fitting of the low dose-response curve by the method of maximum likelihood and calculating
the error of the dose estimate, odds ratio method for cases of suspected exposure to a low dose, a
sample calculation and sample data sheet for recording aberrations.
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/IEC 17025, General requirements for the competence of testing and calibration laboratories
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminological 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
acentric
terminal or interstitial chromosome fragment of varying size, referred to as an excess acentric fragment
when it is formed independently of a dicentric or centric ring chromosome aberration
1
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oSIST prEN ISO 19238:2022
ISO/DIS 19238:2022(E)
3.2
background frequency/level
spontaneous frequency (or number) of chromosome aberrations recorded in control samples or
individuals
3.3
centric ring
aberrant circular chromosome resulting from the joining of two breaks on separate arms of the same
chromosome
Note 1 to entry: It is generally accompanied by an acentric fragment.
3.4
centromere
specialized constricted region of a chromosome that appears during mitosis and joins together the
chromatid pair
3.5
confidence interval
range within which the true value of a statistical quantity lies with a specified probability
3.6
chromosome
structure that comprises discrete packages of DNA and proteins that carry genetic information, and
which condenses to form characteristically shaped bodies during nuclear division
3.7
chromatid
either of the two strands of a duplicated chromosome that are joined by a single centromere and which
separate during cell division to become individual chromosomes
3.8
cytogenetics
A branch of genetics that deals with the study of chromosomes
3.9
dicentric
aberrant chromosome having two centromeres derived from the joining of parts from two broken
chromosomes, generally accompanied by an acentric fragment
3.10
interphase
period of a cell cycle between mitotic divisions
3.11
linear energy transfer (LET)
quotient of the mean energy lost by the charged particles due to electronic interactions in traversing a
distance in the material, minus the mean sum of the kinetic energies in excess of the maximum energy
of electrons locally deposited, of all the electrons released by the charged particles and the distance
traversed
3.12
metaphase
stage of mitosis when the nuclear membrane is dissolved and the chromosomes are condensed to their
minimum lengths and aligned for division
3.13
mitotic index
percentage of cells of a cell population under division at a particular time of observation
2
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oSIST prEN ISO 19238:2022
ISO/DIS 19238:2022(E)
3.14
precision
concept employed to describe dispersion of measurements with respect to a measure of location or
central tendency
3.15
quality assurance (QA)
planned and systematic actions necessary to provide adequate confidence that a process, measurement,
or service satisfies given requirements for quality
3.16
quality control (QC)
planned and systematic actions intended to verify that systems and components conform with
predetermined requirements
3.17
Qdr
Chromosome aberration yield in cells with a chromosome aberration, typically calculated as the number
of dicentrics and/or rings divided by the number of metaphase spreads with either a dicentric or ring
3.18
service laboratory
laboratory performing biological dosimetry measurements
4 Abbreviated terms
BrdU Bromodeoxyuridine
Co Cobalt
covar Covariance
Cs Cesium
FBS Foetal bovine serum
FpG Fluorescence plus Giemsa
Gy Gray
H Null hypothesis
0
H Alternative hypothesis
1
HVL Half value layer
IAEA International Atomic Energy Agency
IEC International Electrochemical Commission
ISO International Organization for Standardization
IU International units
KCl Potassium chloride
LCL Lower confidence limits
MEM Minimum essential medium
3
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oSIST prEN ISO 19238:2022
ISO/DIS 19238:2022(E)
PHA Phytohaemagglutinin
2
...
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