natgillin/translations-raw huggingface dataset:
Tilstrækkeligt antal analyserbare celler og koncentrationer (punkt 31 og 21).
Historical control data
Kriterierne for valg af højeste koncentration er i overensstemmelse med kriterierne i punkt 22, 23 og 24.
The laboratory should establish:
Evaluering og fortolkning af resultater
A historical positive control range and distribution,
Såfremt alle acceptkriterier er opfyldt, anses et testkemikalie for at være klart positivt, hvis følgende er opfyldt i en af de undersøgte forsøgsbetingelser (jf. punkt 28):
A historical negative (untreated, solvent) control range and distribution.
Mindst en af testkoncentrationerne udviser en statistisk signifikant stigning sammenlignet med den sideløbende negative kontrol.
When first acquiring data for an historical negative control distribution, concurrent negative controls should be consistent with published control data, where they exist.
b. stigningen er dosisafhængig, når den evalueres med en passende trend test
As more experimental data are added to the control distribution, concurrent negative controls should ideally be within the 95 % control limits of that distribution (44) (47).
Et eller flere af resultaterne ligger uden for fordelingen af de historiske negative kontroldata (f.eks. Poisson-baserede kontrolgrænser på 95 %, jf. punkt 39).
The laboratory's historical negative control database should initially be built with a minimum of 10 experiments but would preferably consist of at least 20 experiments conducted under comparable experimental conditions.
Når alle disse kriterier er opfyldt, anses testkemikaliet for at kunne fremkalde kromosomaberrationer i de dyrkede pattedyrceller i dette testsystem.
Laboratories should use quality control methods, such as control charts (e.g. C-charts or X-bar charts (48)), to identify how variable their positive and negative control data are, and to show that the methodology is ‘under control’ in their laboratory (44).
Anbefalinger til de mest hensigtsmæssige statistiske metoder kan findes i litteraturen (49) (50) (51).
Further recommendations on how to build and use the historical data (i.e. criteria for inclusion and exclusion of data in historical data and the acceptability criteria for a given experiment) can be found in the literature (47).
Såfremt alle acceptkriterier er opfyldt, anses et testkemikalie for at være klart negativt, hvis følgende er opfyldt i alle de undersøgte forsøgsbetingelser (jf. punkt 28):
Any changes to the experimental protocol should be considered in terms of their consistency with the laboratory's existing historical control databases.
a. ingen af testkoncentrationerne udviser en statistisk signifikant stigning sammenlignet med den sideløbende negative kontrol
Any major inconsistencies should result in the establishment of a new historical control database.
Der indtræder ikke en koncentrationsafhængig stigning, når der foretages en evaluering med en passende trend test.
Negative control data should consist of the incidence of cells with chromosome aberrations from a single culture or the sum of replicate cultures as described in paragraph 21.
Alle resultaterne ligger inden for fordelingen af de historiske negative kontroldata (f.eks. Poisson-baserede kontrolgrænser på 95 %, jf. punkt 39).
Concurrent negative controls should ideally be within the 95 % control limits of the distribution of the laboratory's historical negative control database (44) (47).
Testkemikaliet anses derefter for ikke at kunne fremkalde kromosomaberrationer i de dyrkede pattedyrceller i dette testsystem.
Where concurrent negative control data fall outside the 95 % control limits they may be acceptable for inclusion in the historical control distribution as long as these data are not extreme outliers and there is evidence that the test system is ‘under control’ (see paragraph 37) and evidence of absence of technical or human failure.
Der er ikke krav om verifikation af en klart positiv eller negativ respons.
Presentation of the results
Hvis responsen hverken er klart negativ eller positiv som beskrevet ovenfor eller for at bidrage til at fastslå den biologiske relevans af et resultat, bør dataene evalueres af eksperter, og/eller der bør foretages yderligere undersøgelser.
The percentage of cells with structural chromosomal aberration(s) should be evaluated.
Scoring af yderligere celler (hvor det er relevant) eller et nyt forsøg, eventuelt med ændrede forsøgsbetingelser (f.eks. koncentrationsinterval, andre metabolismeaktiveringsbetingelser (dvs. S9-koncentration eller S9-oprindelse) kan være nyttigt.
Chromatid- and chromosome-type aberrations classified by sub-types (breaks, exchanges) should be listed separately with their numbers and frequencies for experimental and control cultures.
I sjældne tilfælde, selv efter yderligere undersøgelser, giver dataene ikke mulighed for at konkludere, om resultaterne er positive eller negative; konklusionen er derfor, at testkemikalieresponsen er tvetydig.
Gaps are recorded and reported separately but not included in the total aberration frequency.
En forøgelse i antallet af polyploide celler kan være tegn på, at testkemikaliet er i stand til at inhibere mitoseprocesser og fremkalde kromosomantalsaberrationer (52).
Percentage of polyploidy and/or endoreduplicated cells are reported when seen.
En forøgelse af antallet af celler med endofordoblede kromosomer kan være tegn på, at testkemikaliet kan inhibere cellecyklussens forløb (53) (54) (jf. punkt 2).
Concurrent measures of cytotoxicity for all treated, negative and positive control cultures in the main aberration experiment(s) should be recorded.
Forekomsten af polyploide celler og celler med endofordoblede kromosomer bør derfor registreres særskilt.
Individual culture data should be provided.
oprindelse, batchnummer, frist for anvendelse, hvis dette foreligger
Additionally, all data should be summarised in tabular form.
testkemikaliets stabilitet, hvis dette er kendt
Acceptability Criteria
testkemikaliets opløselighed og stabilitet i opløsningsmidlet, hvis dette er kendt
Acceptance of a test is based on the following criteria:
måling af pH-værdi, osmolalitet og bundfald i det dyrkningsmedium, hvortil kemikaliet blev tilsat, hvor det er relevant.
The concurrent negative control is considered acceptable for addition to the laboratory historical negative control database as described in paragraph 39.
Stof med kun en bestanddel:
Concurrent positive controls (see paragraph 26) should induce responses that are compatible with those generated in the historical positive control data base and produce a statistically significant increase compared with the concurrent negative control.
fysisk udseende, vandopløselighed og yderligere relevante fysisk-kemiske egenskaber
Cell proliferation criteria in the solvent control should be fulfilled (paragraphs 17 and 18).
kemisk identifikation, f.eks. IUPAC-navn eller CAS-navn, CAS-nummer, SMILES- eller InChI-kode, strukturformel, renhed, kemisk identitet af urenheder, i det omfang det er relevant og praktisk muligt, osv.
All three experimental conditions were tested unless one resulted in positive results (see paragraph 28).
Stof med flere bestanddele, UVCB-stoffer og blandinger:
Adequate number of cells and concentrations are analysable (paragraphs 31 and 21).
kendetegnet så vidt muligt ved kemisk identitet (jf. ovenfor), kvantitativ forekomst og bestanddelenes relevante fysisk-kemiske egenskaber.
The criteria for the selection of top concentration are consistent with those described in paragraphs 22, 23 and 24.
Opløsningsmiddel:
Evaluation and interpretation of results
begrundelse for valg af opløsningsmiddel
Providing that all acceptability criteria are fulfilled, a test chemical is considered to be clearly positive if, in any of the experimental conditions examined (see paragraph 28):
procentdelen af opløsningsmiddel i det endelige dyrkningsmedium bør også angives.
at least one of the test concentrations exhibits a statistically significant increase compared with the concurrent negative control,
Celler:
the increase is dose-related when evaluated with an appropriate trend test,
celletype og oprindelse
any of the results are outside the distribution of the historical negative control data (e.g. Poisson-based 95 % control limits; see paragraph 39).
den valgte celletypes karyotypiske karakteristika og egnethed
When all of these criteria are met, the test chemical is then considered able to induce chromosomal aberrations in cultured mammalian cells in this test system.
fravær af mycoplasma for cellelinjer
Recommendations for the most appropriate statistical methods can be found in the literature (49) (50) (51).
for cellelinjer, oplysninger om cellecyklussens længde, fordoblingstid eller proliferationsindeks
Providing that all acceptability criteria are fulfilled, a test chemical is considered clearly negative if, in all experimental conditions examined (see paragraph 28):
bloddonorers køn, alder og andre relevante oplysninger om donor, fuldblod eller fraseparerede lymfocytter, benyttet mitogen
none of the test concentrations exhibits a statistically significant increase compared with the concurrent negative control,
eventuelt antal passager for cellelinjer
there is no concentration-related increase when evaluated with an appropriate trend test,
eventuelle metoder til opbevaring af cellekulturer for cellelinjer
all results are inside the distribution of the historical negative control data (e.g. Poisson-based 95 % control limits; see paragraph 39).
normalt kromosomtal for cellelinjer.
The test chemical is then considered unable to induce chromosomal aberrations in cultured mammalian cells in this test system.
Testbetingelser:
There is no requirement for verification of a clearly positive or negative response.
det metafasestandsende kemikalies betegnelse og koncentration og varigheden af cellernes eksponering for stoffet
In case the response is neither clearly negative nor clearly positive as described above or in order to assist in establishing the biological relevance of a result, the data should be evaluated by expert judgement and/or further investigations.
testkemikaliets koncentration udtrykt som endelig koncentration i dyrkningsmediet (f.eks. μg eller mg/ml eller mM af dyrkningsmediet)
Scoring additional cells (where appropriate) or performing a repeat experiment possibly using modified experimental conditions (e.g. concentration spacing, other metabolic activation conditions (i.e. S9 concentration or S9 origin)) could be useful.
begrundelse for valg af koncentrationer og antal kulturer, herunder f.eks. cytotoksicitetsdata og opløselighedsbegrænsninger
In rare cases, even after further investigations, the data set will preclude making a conclusion of positive or negative results, and therefore the test chemical response will be concluded to be equivocal.
substratsammensætning og eventuel CO2-koncentration, fugtighedsniveau
An increase in the number of polyploid cells may indicate that the test chemicals have the potential to inhibit mitotic processes and to induce numerical chromosomal aberrations (52).
koncentration (og/eller volumen) af opløsningsmiddel og tilsat testkemikalie i dyrkningsmediet
An increase in the number of cells with endoreduplicated chromosomes may indicate that the test chemicals have the potential to inhibit cell cycle progress (53) (54) (see paragraph 2).
inkubationstemperatur
Therefore, incidence of polyploid cells and cells with endoreduplicated chromosomes should be recorded separately.
inkubationstid
source, lot number, limit date for use, if available
behandlingens varighed
stability of the test chemical itself, if known;
høsttidspunkt efter behandling
solubility and stability of the test chemical in solvent, if known.
celletæthed ved udsåning, hvis det er relevant
measurement of pH, osmolality and precipitate in the culture medium to which the test chemical was added, as appropriate.
metabolismeaktiveringssystemets type og sammensætning (kilde for S9, metode til fremstilling af S9-sammensætning, koncentration eller rumfang af S9-blanding og S9 i det endelige dyrkningsmedium, kvalitetskontrol af S9)
Mono-constituent substance:
positive og negative kontrolkemikalier, endelige koncentrationer for hver behandlingsbetingelse
physical appearance, water solubility, and additional relevant physicochemical properties;
anvendte metoder til præparering af objektglas og farvningsteknik
chemical identification, such as IUPAC or CAS name, CAS number, SMILES or InChI code, structural formula, purity, chemical identity of impurities as appropriate and practically feasible, etc.
kriterier for accept af assays
Multi-constituent substance, UVCBs and mixtures:
kriterier for scoring af aberrationer
characterised as far as possible by chemical identity (see above), quantitative occurrence and relevant physicochemical properties of the constituents.
antal analyserede metafaser
Solvent:
metoder til måling af cytotoksicitet
justification for choice of solvent.
eventuelle supplerende oplysninger vedrørende cytotoksicitet og anvendt metode
percentage of solvent in the final culture medium should also be indicated.
kriterier for bedømmelse af undersøgelsen som positiv, negativ eller tvetydig
Cells:
anvendte metoder til bestemmelse af pH, osmolalitet og bundfald.
type and source of cells
antal behandlede celler og antal høstede celler for hver kultur, når der benyttes cellelinjer
karyotype features and suitability of the cell type used;
cytotoksicitetsmålinger, f.eks. RPD, RICC, MI og eventuelt andre observationer
absence of mycoplasma, for cell lines;
oplysninger om cellecyklussens længde, fordoblingstid eller proliferationsindeks for cellelinjer
for cell lines, information on cell cycle length, doubling time or proliferation index;
tegn på bundfald og tidspunkt for bestemmelse
sex of blood donors, age and any relevant information on the donor, whole blood or separated lymphocytes, mitogen used;
definitioner af aberrationer, herunder gaps
number of passages, if available, for cell lines;
antal scorede celler, antal celler med kromosomaberrationer og typen af disse, anført særskilt for hver behandlet kultur og kontrolkultur med og uden gaps
methods for maintenance of cell cultures, for cell lines;
eventuelt observerede ploidiændringer (polyploide celler og celler med endofordoblede kromosomer, anført særskilt)
modal number of chromosomes, for cell lines.
koncentration/respons-sammenhængen, når det er muligt
Test conditions:
sideløbende negative (opløsningsmiddel) og positive kontrolprøver (koncentrationer og opløsningsmidler)
identity of the metaphase-arresting chemical, its concentration and duration of cell exposure;
historisk negative (opløsningsmiddel) og positive kontroldata med angivelse af intervaller, gennemsnit og standardafvigelser og kontrolgrænser på 95 % for fordelingen, samt mængden af data
concentration of test chemical expressed as final concentration in the culture medium (e.g. μg or mg/mL or mM of culture medium).
statistiske analyser og eventuelle P-værdier.
rationale for selection of concentrations and number of cultures including, e.g. cytotoxicity data and solubility limitations;
Diskussion af resultater.
composition of media, CO2 concentration if applicable, humidity level;
Konklusioner.
concentration (and/or volume) of solvent and test chemical added in the culture medium;
, “Cytological Methods for Detecting Chemical Mutagens”, in Chemical Mutagens, Principles and Methods for their Detection, Vol. 4, Hollaender, A. (ed.), Plenum Press, New York and London, pp.
incubation temperature;
1-29.
incubation time;
Ishidate, M. Jr., T. Sofuni (1985), “The in vitro Chromosomal Aberration Test Using Chinese Hamster Lung (CHL) Fibroblast Cells in Culture” in Progress in Mutation Research, Vol. 5, Ashby, J. et al. (eds.), Elsevier Science Publishers, Amsterdam-New York- Oxford, pp.
duration of treatment;
427-432.
harvest time after treatment;
, Improving dose selection and identification of aneugens in the in vitro chromosome aberration test by integration of flow cytometry-based methods, Environmental and Molecular Mutagenesis, Vol. 49/4, pp.
cell density at seeding, if appropriate;
318-327.
type and composition of metabolic activation system (source of S9, method of preparation of the S9 mix, the concentration or volume of S9 mix and S9 in the final culture medium, quality controls of S9);
Kapitel B.49 i dette bilag: In vitro-mikrokernetest i pattedyrceller.
positive and negative control chemicals, final concentrations for each conditions of treatment;
, “A Safe Substitute for Polychlorinated Biphenyls as an Inducer of Metabolic Activation Systems”, in In Vitro Metabolic Activation in Mutagenesis Testing, de Serres, F.J. et al. (eds.), Elsevier, North-Holland, pp.
methods of slide preparation and staining technique used;
85-88.
criteria for acceptability of assays;
Tilgængelig på: http://www.pops.int/.
criteria for scoring aberrations;
McCooey (1982), “CHO/HGPRT Mutation Assay: Evaluation of Gases and Volatile Liquids”, in Genotoxic Effects of Airborne Agents, Tice, R.R., D.L. Costa, K.M.
number of metaphases analysed;
Schaich (eds.), Plenum, New York, pp.
methods for the measurements of cytotoxicity;
91-103.
any supplementary information relevant to cytotoxicity and method used;
I: Statistical Evaluation of Mutagenicity Test Data, Kirkland, D.J. (ed.)
criteria for considering studies as positive, negative or equivocal;
Cambridge University Press, Cambridge, pp.
methods used to determine pH, osmolality and precipitation.
141-154.
the number of cells treated and the number of cells harvested for each culture when cell lines are used
Tilgængelig på anmodning.
cytotoxicity measurements, e.g. RPD, RICC, MI, other observations if any;
Tilgængelig på: https://federalregister.gov/a/2012-13774.
information on cell cycle length, doubling time or proliferation index in case of cell lines;
, “Analysis of Data from In Vitro Cytogenetic Assays”, in Statistical Evaluation of Mutagenicity Test Data, Kirkland, D.J. (ed.), Cambridge University Press, Cambridge, pp.
changes in ploidy (polyploid cells and cells with endoreduplicated chromosomes, given separately) if seen;
141-154.
concentration-response relationship, where possible;
Tillæg 1
concurrent negative (solvent) and positive control data (concentrations and solvents);
DEFINITIONER
historical negative (solvent) and positive control data, with ranges, means and standard deviations and 95 % control limits for the distribution, as well as the number of data;
Aneuploidi
statistical analyses, p-values if any.
Enhver afvigelse fra det normale diploide (eller haploide) kromosomtal af et eller flere kromosomer, men ikke af et eller flere komplette kromosomsæt (polyploidi).
Discussion of the results.
Apoptose
Conclusions.
Programmeret celledød karakteriseret ved en række trin, der forårsager opløsning af celler i membranbundne partikler, som herefter elimineres ved fagocytose eller afstødning.
Overview of the set of OECD Genetic Toxicology Test Guidelines and updates performed in 2014-2015.
Celleproliferation
ENV Publications.
Forøgelse af celleantal som følge af mitotisk celledeling.
Series on Testing and Assessment, No. 234, OECD, Paris.
Et stof eller en blanding.
, “Cytological Methods for Detecting Chemical Mutagens”, in Chemical Mutagens, Principles and Methods for their Detection, Vol.
Kromatidbrud
4, Hollaender, A. (ed.), Plenum Press, New York and London, pp. 1-29
Diskontinuitet i et enkelt kromatid, hvor der er en tydelig forskydning af en af kromatiderne.
Ishidate, M. Jr., T. Sofuni (1985), “The in vitro Chromosomal Aberration Test Using Chinese Hamster Lung (CHL) Fibroblast Cells in Culture” in Progress in Mutation Research, Vol.
Kromatidgap
5, Ashby, J. et al.
Region uden farvning (akromatisk læsion) af et enkeltkromatid, hvor der er minimal forskydning af kromatidet.
(eds.), Elsevier Science Publishers, Amsterdam-New York- Oxford, pp. 427-432.
Aberration af kromatidtypen
, “Improving dose selection and identification of aneugens in the in vitro chromosome aberration test by integration of flow cytometry-based methods”, Environmental and Molecular Mutagenesis, Vol.
Beskadigelse af kromosomstrukturen i form af brud på enkeltkromatider eller brud på og sammenføjning af kromatider.
49/4, pp. 318-327.
Aberration af kromosomtypen
Chapter B.49 of this Annex: In Vitro Mammalian Cell Micronucleus Test.
Beskadigelse af kromosomstrukturen i form af brud på — eller brud på og sammenføjning af — begge kromatider på samme sted.
, “A Safe Substitute for Polychlorinated Biphenyls as an Inducer of Metabolic Activation Systems”, in In Vitro Metabolic Activation in Mutagenesis Testing, de Serres, F.J. et al.
Klastogen
(eds.), Elsevier, North-Holland, pp. 85-88.
Alle stoffer eller processer, der forårsager strukturelle kromosomaberrationer i populationer af celler eller organismer.
Available at: http://www.pops.int/.
Koncentrationer
McCooey (1982), “CHO/HGPRT Mutation Assay: Evaluation of Gases and Volatile Liquids”, in Genotoxic Effects of Airborne Agents, Tice, R.R., D.L.
Henviser til endelige koncentrationer af testkemikaliet i dyrkningsmediet.
Costa, K.M.
Cytotoksicitet
Schaich (eds.), Plenum, New York, pp. 91-103.
Endofordobling
In: Statistical Evaluation of Mutagenicity Test Data, Kirkland, D.J.
En proces, hvorved cellekernen efter en S-fase i DNA-replikationen ikke fortsætter over i mitosen, men påbegynder endnu en S-fase.
(ed.)
Resultatet er kromosomer med 4, 8, 16, ... kromatider.
Cambridge University Press, Cambridge, pp. 141-154.
Genotoksisk
Available upon request.
Generelt udtryk, der omfatter alle former for DNA- eller kromosombeskadigelse, herunder brud, deletioner, addukter, ændringer af nukleotider og koblinger, omlejringer, genmutationer, kromosomaberrationer og aneuploidi.
Available at: https://federalregister.gov/a/2012-13774.
Det er ikke alle former for genotoksiske virkninger, der forårsager mutationer eller stabil kromosomskade.
OECD (2014), “Statistical analysis supporting the revision of the genotoxicity Test Guidelines, OECD Environment, Health and Safety Publications (EHS)”, Series on Testing and Assessment, No. 198, OECD Publishing, Paris.
Mitoseindeks (MI)
, “Metaphase chromosome aberration assays in vitro”, in Basic Mutagenicity Tests: UKEMS Recommended Procedures, Kirkland, D.J.
Forholdet mellem antallet af celler i metafase og det samlede antal celler i en population; viser populationens formeringsgrad.
(ed.), Cambridge University Press, Cambridge, pp. 62-86.
Mitose
, “Analysis of Data from In Vitro Cytogenetic Assays”, in Statistical Evaluation of Mutagenicity Test Data, Kirkland, D.J.
Deling af cellekernen, der normalt inddeles i profase, prometafase, metafase, anafase og telofase.
(ed.), Cambridge University Press, Cambridge, pp. 141-154.
Mutagen
Appendix 1
Forårsager arvelige ændringer af DNA-baseparsekvens(er) i gener eller i kromosomstrukturen (kromosomaberrationer).
DEFINITIONS
Antalsaberration
Aneuploidy
Ændring af kromosomtallet i forhold til det for de pågældende celler normale antal.
any deviation from the normal diploid (or haploid) number of chromosomes by a single chromosome or more than one, but not by entire set(s) of chromosomes (polyploidy).
Polyploidi
Apoptosis
Antalsmæssige kromosomaberrationer i celler eller organismer, der involverer et eller flere komplette kromosomsæt, men ikke et enkelt kromosom eller kromosomer (aneuploidi).
programmed cell death characterised by a series of steps leading to a disintegration of cells into membrane-bound particles that are then eliminated by phagocytosis or by shedding.
p53-status
Cell proliferation
p53-protein indgår i cellecyklusregulering, apoptose og DNA-reparation.
increase in cell number as a result of mitotic cell division.
Relativ forøgelse af celletal (RICC)
Chromatid break
Forøgelse af celletallet i kemisk eksponerede kulturer i forhold til forøgelsen i ubehandlede kulturer udtrykt i procent.
discontinuity of a single chromatid in which there is a clear misalignment of one of the chromatids.
Relativ populationsfordobling (RPD)
Chromatid gap
Forøgelse af antallet af populationsfordoblinger i kemisk eksponerede kulturer i forhold til forøgelsen i ubehandlede kulturer udtrykt i procent.
non-staining region (achromatic lesion) of a single chromatid in which there is minimal misalignment of the chromatid.
S9-leverfraktion
Chromatid-type aberration