natgillin/translations-raw huggingface dataset:
det metafasestandsende stofs betegnelse og koncentration og længden af cellernes udsættelse for stoffet
identity of metaphase arresting substance, its concentration and duration of cell exposure,
begrundelse for valg af koncentrationer og antal kulturer, herunder f.eks. eventuelle cytotoksicitetsdata og opløselighedsbegrænsninger
rationale for selection of concentrations and number of cultures including, e.g. cytotoxicity data and solubility limitations, if available,
substratsammensætning og eventuel CO2-koncentration
composition of media, CO2 concentration if applicable,
teststoffets koncentration
concentration of test substance,
volumen af tilsat bærestof og teststof
volume of vehicle and test substance added,
inkuberingstemperatur
incubation temperature,
inkuberingstid
incubation time,
behandlingens varighed
duration of treatment,
celletæthed ved udsåning, hvis det er relevant
cell density at seeding, if appropriate,
metabolismeaktiveringssystemets type og sammensætning, herunder acceptkriterier
type and composition of metabolic activation system, including acceptability criteria,
positiv og negativ kontrol
positive and negative controls,
metoder til præparering af objektglas
methods of slide preparation,
kriterier for bedømmelse af aberrationer
criteria for scoring aberrations,
antal analyserede metafaser
number of metaphases analysed,
metoder til måling af toksicitet
methods for the measurements of toxicity,
kriterier for bedømmelse af undersøgelsen som positiv, negativ eller tvetydig
criteria for considering studies as positive, negative or equivocal.
tegn på toksicitet, f.eks. konfluens, cellecyklusdata, celletælling og mitoseindeks
signs of toxicity, e.g. degree of confluency, cell cycle data, cell counts, mitotic index,
tegn på udfældning
signs of precipitation,
data om pH og osmolalitet i behandlingsmediet, hvis disse værdier er målt
data on pH and osmolality of the treatment medium, if determined,
definitioner af aberrationer, herunder gaps
definition for aberrations, including gaps,
antal celler med kromosomaberrationer og typen af disse, anført særskilt for hver behandlet kultur og kontrolkultur
number of cells with chromosome aberrations and type of chromosome aberrations given separately for each treated and control culture,
eventuel iagttaget ændring i ploidigrad
changes in ploidy if seen,
dosis/respons-sammenhæng, når det er muligt
dose-response relationship, where possible,
eventuelle statistiske analyser
statistical analyses, if any,
data for sideløbende negative (opløsningsmiddel/bærestof) og positive kontrolprøver
concurrent negative (solvent/vehicle) and positive control data,
data for tidligere negative (opløsningsmiddel/bærestof) og positive kontrolprøver med angivelse af intervaller, gennemsnit og standardafvigelser
historical negative (solvent/vehicle) and positive control data, with ranges, means and standard deviations.
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Evans, H. J., (1976) Cytological Methods for Detecting Chemical Mutagens.
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Progress in Mutation Research, Vol. 5, Ashby, J. et al., (Eds) Elsevier Science Publishers, Amsterdam-New York-Oxford, p. 427-432.
Mutaden 10 (suppl. 10), pp. 1-175.
Mutagen 10 (suppl. 10), p. 1-175.
Scott, D., Galloway, S.M., Marshall, R.R., Ishidate, M. Jr., Brusick, D., Ashby, J. and Myhr, B.C. (1991), Genotoxicity under Extreme Culture Conditions.
Scott, D., Galloway, S.M., Marshall, R.R., Ishidate, M.Jr., Brusick, D., Ashby, J. and Myhr, B.C., (1991) Genotoxicity under Extreme Culture Conditions.
A report from ICPEMC Task Group 9, Mutation Res., 257, pp.
A report from ICPEMC Task Group 9.
Maron, D.M. and Arnes, B.N.
Maron, D.M. and Ames, B.N., (1983) Revised Methods for the Salmonella Mutagenicity Test.
(1983), Revised Methods for the Salmonella Mutagenicity Test, Mutation Res., 113, pp. 173-215.
Mutation Res., 113, p. 173-215.
Natarajan.
Natarajan, A.T., Tates, A.D., van Buul, P.P.W., Meijers, M. and de Vogel, N., (1976) Cytogenetic Effects of Mutagen/Carcinogens after Activation in a Microsomal System in Vitro, I. Induction of Chromosome Aberrations and Sister Chromatid Exchange by Diethylnitrosamine (DEN) and Dimethylnitrosamine (DMN) in CHO Cells in the Presence of Rat-Liver Microsomes.
A.T., Tates, A.D., van Buul, P.P.W., Meijers, M. and de Vogel, N. (1976), Cytogenetic Effects of Mutagen/Carcinogens after Activation in a Microsomal System In Vitro, J. Induction of Chromosome Aberrations and Sister Chromatid Exchange by Diethylnitrosamine (DEN) and Dimethylnitrosamine (DMN) in CHO Cells in the Presence of Rat-Liver Microsomes, Mutation Res., 37, pp. 83-90.
Mutation Res., 37, p. 83-90.
Matsuoka, A., Hayashi, M. and Ishidate, M. Jr.
Matsuoka, A., Hayashi, M. and Ishidate, M. Jr., (1979) Chromosomal Aberration Tests on 29 Chemicals Combined with S9 Mix In Vitro.
(1979), Chromosomal Aberration Tests on 29 Chemicals Combined with S9 Mix In Vitro, Mutation Res., 66, pp. 277-290.
Mutation Res., 66, p. 277-290.
Elliot, B.M., Combes. R.D., Elcombe, C.R., Gatehouse, D,G., Gibson, G.G., Mackay, J.M. and Wolf, R.C.
Elliot, B.M., Combes, R.D., Elcombe, C.R., Gatehouse, D.G., Gibson, G.G., Mackay, J.M. and Wolf, R.C., (1992).
(1992), Alternatives to Aroclor 1254-Induced S9 in In Vitro Genotoxicity Assays, Mutagenesis, 7, pp. 175-177.
Mutagenesis, 7, p. 175-177.
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Soper, K.A. and Galloway, S.M.
Soper, K.A. and Galloway, S.M., (1994) Replicate Flasks are not Necessary for In Vitro Chromosome Aberration Assays in CHO Cells.
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Mutation Res., 312, p. 139-149.
Krahn, D.F., Barsky, F.C. and McCooey, K.T.
Krahn, D.F., Barsky, F.C. and McCooey, K.T., (1982) CHO/HGPRT Mutation Assay: Evaluation of Gases and Volatile Liquids.
In: Tice, R.R., Costa, D.I., Schaich, K.M.
Tice, R.R., Costa, D.L., Schaich, K.M.
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Cancer Res., 43, p. 1362-1364.
Denne metode er en gengivelse af OECD Test Guideline 475 Mammalian Bone Marrow Chromosome Aberration Test (1997).
This method is a replicate of the OECD TG 475, Mammalian Bone Marrow Chromosome Aberration Test (1997).
In vitro-testen for kromosomaberrationer hos pattedyr benyttes til at påvise, om et teststof forårsager strukturelle kromosomafvigelser i knoglemarvceller hos dyr, normalt gnavere (1) (2) (3) (4).
The mammalian in vivo chromosome aberration test is used for the detection of structural chromosome aberrations induced by the test substance to the bone marrow cells of animals, usually rodents (1)(2)(3)(4).
Der er to typer strukturændringer, kromosomtypen og kromatidtypen.
Structural chromosome aberrations may be of two types, chromosome or chromatid.
Kromosommutationer og lignende er årsag til mange genetiske sygdomme hos mennesker, og meget tyder på, at kromosommutationer og lignende, som ændrer på onkogener og tumorsuppressorgener i somatiske celler, medvirker ved induktion af kræft hos mennesker og i forsøgssystemet.
Chromosome mutations and related events are the cause of many human genetic diseases and there is substantial evidence that chromosome mutations and related events causing alterations in oncogenes and tumour-suppressor genes are involved in cancer in humans and experimental systems.
Der benyttes rutinemæssigt gnavere i denne test.
Rodents are routinely used in this test.
Knoglemarv er målvævet i denne test, da det er et væv med høj vaskularisation og består af celler med kort cyklustid, som er lette at isolere og behandle. Metoden omfatter ikke andre arter og væv.
Bone marrow is the target tissue in this test, since it is a highly vascularised tissue, and it contains a population of rapidly cycling cells that can be readily isolated and processed.
En in vivo-test er ligeledes nyttig til yderligere undersøgelse af mutagene virkninger, der er påvist ved en in vitro-test.
An in vivo test is also useful for further investigation of a mutagenic effect detected by in vitro test.
Hvis der er grund til at tro, at teststoffet eller en reaktiv metabolit ikke vil nå frem til målvævet, er denne test ikke egnet.
If there is evidence that the test substance, or a reactive metabolite, will not reach the target tissue, it is not appropriate to use this test.
Resultatet er kromosomer med 4, 8, 16, ... kromatider.
The result is chromosomes with four, eight, 16, ...chromatids.
Gap: en akromatisk beskadigelse, som er mindre end ét kromatid bred, og hvor misalignment af kromatiderne er minimal.
Gap: an achromatic lesion smaller than the width of one chromatid, and with minimum misalignment of the chromatid(s).
Dyrene udsættes for teststoffet på passende måde og aflives efter passende tidsrum efter eksponeringen.
Animals are exposed to the test substance by an appropriate route of exposure and are sacrificed at appropriate times after treatment.
Inden aflivningen behandles dyrene med et metafasestandsende stof (f.eks. colchicin eller Colcemid®).
Prior to sacrifice, animals are treated with a metaphase arresting agent (e.g. Colcemid® or colchicine).
Der fremstilles derefter præparater af knoglemarvceller, som farves, og metafasecellerne undersøges for kromosomaberrationer.
Chromosome preparations are then made from the bone marrow cells and stained, and metaphase cells are analysed for chromosome aberrations.
Der benyttes sædvanligvis rotter, mus og kinesiske hamstere, selv om andre egnede pattedyrarter kan benyttes.
Rats, mice and Chinese hamsters are commonly used, although any appropriate mammalian species may be used.
Ved undersøgelsens begyndelse bør vægtvariationen mellem dyrene være mindst mulig og ikke over ±20 % af gennemsnitsvægten for hvert køn.
At the commencement of the study, the weight variation of animals should be minimal and not exceed ± 20 % of the mean weight of each sex.
Der gælder de almindelige forhold som beskrevet i den generelle indledning til del B, blot bør der tilstræbes en fugtighed på 50-60 %.
General conditions referred in the General introduction to Part B are applied although the aim for humidity should be 50-60 %.
Dyrene identificeres entydigt.
The animals are identified uniquely.
Dyrene tilvænnes til laboratorieforholdene i mindst fem dage.
The animals are acclimated to the laboratory conditions for at least five days.
Teststoffer i fast form opløses eller opslæmmes i passende opløsningsmidler eller bærestoffer og fortyndes passende, inden de gives til dyrene.
Solid test substances should be dissolved or suspended in appropriate solvents or vehicles and diluted, if appropriate, prior to dosing of the animals.
Teststoffer i væskeform kan enten gives direkte til dyrene eller fortyndes først.
Liquid test substances may be dosed directly or diluted prior to dosing.
Opløsningsmiddel/bærestof
Solvent/Vehicle
Opløsningsmiddel/bærestof må ikke have toksiske virkninger ved de benyttede doser og må ikke mistænkes for at reagere kemisk med teststoffet.
The solvent/vehicle should not produce toxic effects at the dose levels used, and should not be suspected of chemical reaction with the test substance.
Benyttes der andre opløsningsmidler/bærestoffer end de velkendte, skal brugen af dem underbygges med kompatibilitetsdata.
If other than well-known solvents/vehicles are used, their inclusion should be supported with data indicating their compatibility.
Det anbefales i videst muligt omfang først at forsøge at benytte et vandigt opløsningsmiddel/bærestofsystem.
It is recommended that wherever possible, the use of an aqueous solvent/vehicle should be considered first.
I alle forsøg medtages der sideløbende både positive og negative (opløsningsmiddel eller bærestof) kontrolgrupper af begge køn.
Concurrent positive and negative (solvent/vehicle) controls should be included for each sex in each test.
Bortset fra behandling med teststof skal dyrene i kontrolgrupperne behandles på samme måde som dyrene i behandlingsgrupperne.
Except for treatment with the test substance, animals in the control groups should be handled in an identical manner to the animals in the treated groups.
Positive kontrolprøver skal frembringe strukturelle ændringer in vivo ved en dosis, der forventes at give en påviselig forøgelse i forhold til baggrundsværdierne.
Positive controls should produce structural aberrations in vivo at exposure levels expected to give a detectable increase over background.
Der vælges sådanne doser i de positive kontrolprøver, at virkningerne er tydelige, uden dog at de kodede objektglas' identitet umiddelbart afsløres for den, der aflæser dem.
Positive control doses should be chosen so that the effects are clear but do not immediately reveal the identity of the coded slides to the reader.
Det kan accepteres, at den positive kontrol indgives på anden måde end teststoffet, og at der kun foretages én prøveudtagning.
It is acceptable that the positive control be administered by a route different from the test substance and sampled at only a single time.
Hvis der er mulighed for det, bør der anvendes kemisk beslægtede stoffer.
The use of chemical class related positive control chemicals may be considered, when available.
Triethylenmelamin
Triethylenemelamine
Der skal ved hver prøveudtagning indgå negative kontrolgrupper, som kun er behandlet med opløsningsmiddel eller bærestof, og ellers behandlet på samme måde som behandlingsgrupperne, medmindre tidligere kontroldata har vist en acceptabel variation mellem dyr og hyppighed af celler med kromosomafvigelser.
Negative controls, treated with solvent or vehicle alone, and otherwise treated in the same way as the treatment groups, should be included for every sampling time, unless acceptable inter-animal variability and frequencies of cells with chromosome aberrations are available from historical control data.
Hvis der kun udtages én negativ kontrolprøve, er det mest hensigtsmæssigt at gøre det ved første prøveudtagning.
If single sampling is applied for negative controls, the most appropriate time is the first sampling time.
Desuden skal der være ubehandlede kontrolgrupper, medmindre der foreligger tidligere opnåede eller offentliggjorte kontroldata, der viser, at det valgte opløsningsmiddel ingen skadelige eller mutagene virkninger har.
In addition, untreated controls should also be used unless there are historical or published control data demonstrating that no deleterious or mutagenic effects are induced by the chosen solvent/vehicle.
Dyrenes antal og køn
Number and sex of animals
Hver behandlet gruppe og kontrolgruppe skal bestå af mindst fem analyserbare dyr af hvert køn.
Each treated and control group must include at least five analysable animals per sex.
Hvis der på det tidspunkt, hvor undersøgelsen foretages, foreligger data fra undersøgelser med samme dyreart og med samme indgiftsmåde, som viser, at der ikke er nogen væsentlig toksicitetsforskel mellem de to køn, er test med kun ét køn tilstrækkeligt.
If at the time of the study there are data available from studies in the same species and using the same route of exposure that demonstrate that there are no substantial differences in toxicity between sexes, then testing in a single sex will be sufficient.
Hvis udsættelsen af mennesker for det kemiske stof er kønsspecifik, som det f.eks. er tilfældet med visse farmaceutiske stoffer, skal testen udføres med dyr af det pågældende køn.
Where human exposure to chemicals may be sex-specific, as for example with some pharmaceutical agents, the test should be performed with animals of the appropriate sex.
Behandlingsplan
Treatment schedule
Teststofferne indgives fortrinsvis i en enkelt dosis.
Test substances are preferably administered as a single treatment.
De kan også indgives i to deldoser, dvs. to behandlinger samme dag med kun nogle få timers interval, hvorved det bliver lettere at indgive et større materialevolumen.
Test substances may also be administered as a split dose, i.e. two treatments on the same day separated by no more than a few hours, to facilitate administering a large volume of material.
Indgift på anden måde skal begrundes sagligt.
Other dose regimens should be scientifically justified.
Der udtages prøver på to tidspunkter efter endagsbehandling.
Samples should be taken at two separate times following treatment on one day.
For gnavere udtages første prøve normalt 1,5 normal cellecykluslængde (som normalt er 12-18 timer) efter behandlingen.
For rodents, the first sampling interval is 1,5 normal cell cycle length (the latter being normally 12-18 hr) following treatment.
Da det optimale tidspunkt for påvisning af kromosomaberrationer kan afhænge af, hvor lang tid der er påkrævet for optagelse og metabolisme af teststoffet, og af teststoffets indvirkning på cellecyklussens kinetik, anbefales det at udtage endnu en prøve 24 timer efter den første.
Since the time required for uptake and metabolism of the test substance as well as its effect on cell cycle kinetics can affect the optimum time for chromosome aberration detection, a later sample collection 24 hr after the first sample time is recommended.
Indgives stoffet over mere end én dag, udtages der blot én prøve, når der er gået 1,5 normal cellecykluslængde efter den sidste behandling.
If dose regimens of more than one day are used, one sampling time at 1,5 normal cell cycle lengths after the final treatment should be used.
Inden aflivningen gives dyrene en intraperitoneal injektion med en passende dosis metafasestandsende stof (f.eks. Colcemid® eller colchicin).
Prior to sacrifice, animals are injected intraperitoneally with an appropriate dose of a metaphase arresting agent (e.g. Colcemid® or colchicine).
Der udtages prøver af forsøgsdyr efter et passende tidsrum.
Animals are sampled at an appropriate interval thereafter.
For mus er dette tidsrum ca. tre-fem timer, for kinesisk hamster ca. fire-fem timer.
For mice this interval is approximately three to five hours; for Chinese hamsters this interval is approximately four to five hours.
Cellerne høstes fra knoglemarven og analyseres for kromosomaberrationer.
Cells are harvested from the bone marrow and analysed for chromosome aberrations.
Hvis der gennemføres en forprøve til bestemmelse af dosisinterval, fordi der ikke foreligger nogen egnede data, bør den udføres i samme laboratorium med samme art, stamme, køn og behandlingsmåde, som agtes benyttet i hovedundersøgelsen (5).
If a range finding study is performed because there are no suitable data available, it should be performed in the same laboratory, using the same species, strain, sex and treatment regimen to be used in the main study (5).
Er der tale om toksicitet, benyttes der tre dosisniveauer for første prøveudtagningstidspunkt.
If there is toxicity, three dose levels are used for the first sampling time.
Disse dosisniveauer skal dække et interval fra maksimal toksicitet til næsten ingen eller ingen toksicitet.
These dose levels should cover a range from the maximum to little or no toxicity.
Ved den efterfølgende prøveudtagning behøves kun den højeste dosis benyttet.
At the later sampling time only the highest dose needs to be used.
Den højeste dosis defineres som den dosis, der fremkalder sådanne tegn på toksicitet, at højere dosis med samme indgiftsmønster må forventes at medføre død.
The highest dose is defined as the dose producing signs of toxicity such that higher dose levels, based on the same dosing regimen, would be expected to produce lethality.
Stoffer med specifik biologisk aktivitet ved lav ikke-toksisk dosis (f.eks. hormoner og mitogener) kan danne undtagelser fra disse dosisfastsættelseskriterier og bør evalueres individuelt.
Substances with specific biological activities at low non-toxic doses (such as hormones and mitogens) may be exceptions to the dose-setting criteria and should be evaluated on a case-by-case basis.
Højeste dosis kan også defineres som en dosis, der i nogen grad udviser tegn på toksicitet i knoglemarven (f.eks. mitoseindeks nedsat med mere end 50 %).
The highest dose may also be defined as a dose that produces some indication of toxicity in the bone marrow (e.g. greater than 50 % reduction in mitotic index).
Hvis der ved en test med én dosis på mindst 2000 mg/kg legemsvægt indgivet på én gang eller i to omgange samme dag ikke kan iagttages nogen toksiske virkninger, og hvis man på grundlag af data om strukturmæssigt beslægtede stoffer ikke forventer gentoksicitet, kan en fuldstændig undersøgelse med tre dosisniveauer anses for unødvendig.
If a test at one dose level of at least 2000 mg/kg body weight using a single treatment, or as two treatments on the same day, produces no observable toxic effects, and if genotoxicity would not be expected based on data from structurally related substances, then a full study using three dose levels may not be considered necessary.
For længerevarende undersøgelser er grænsedosis på 2000 mg/kg legemsvægt pr. dag for behandlinger over højst 14 dage og på 1000 mg/kg legemsvægt pr. dag for behandlinger over mere end 14 dage.
For studies of a longer duration, the limit dose is 2000 mg/kg/body weight/day for treatment up to 14 days, and 1000 mg/kg/body weight/day for treatment longer than 14 days.
Den forventede eksponering af mennesker kan foranledige, at der benyttes en højere dosis i grænsetesten.
Expected human exposure may indicate the need for a higher dose level to be used in the limit test.
Teststoffet indgives normalt ved tvangsfodring med sonde eller en passende intubationskanyle eller ved intraperitoneal injektion.
The test substance is usually administered by gavage using a stomach tube or a suitable intubation cannula, or by intraperitoneal injection.
Andre indgiftsmåder kan accepteres, hvis de kan begrundes.
Other routes of exposure may be acceptable where they can be justified.
Hvor stor en væskemængde, der kan indgives ad gangen ved tvangsfodring eller injektion, afhænger af forsøgsdyrenes størrelse.
The maximum volume of liquid that can be administered by gavage or injection at one time depends on the size of the test animal.
Mængden bør højst være på 2 ml pr. 100 g legemsvægt.
The volume should not exceed 2 ml/100 g body weight.
Anvendelse af større rumfang skal begrundes.
The use of volumes higher than these must be justified.