natgillin/translations-raw huggingface dataset:
Cornea-uklarhed måles kvantitativt som mængden af lystransmission gennem cornea.
Serious eye damage is the production of tissue damage in the eye, or serious physical decay of vision, following application of a test chemical to the anterior surface of the eye, which is not fully reversible within 21 days of application.
Permeabilitet måles kvantitativt som mængden af farvestoffet natriumfluorescein, der passerer gennem den fulde tykkelse af cornea som påvist i mediet i det bageste kammer.
Test chemicals inducing serious eye damage are classified as UN GHS Category 1.
Testkemikalierne tilføres til cornea-epiteloverfladen ved tilsætning til corneaholderens forreste kammer.
Chemicals not classified for eye irritation or serious eye damage are defined as those that do not meet the requirements for classification as UN GHS Category 1 or 2 (2A or 2B), i.e. they are referred to as UN GHS No Category.
I tillæg 4 findes en beskrivelse af og et diagram over en corneaholder, som anvendes i BCOP-forsøgsmetoden.
This test method includes the recommended use and limitations of the BCOP test method based on its evaluations.
Corneaholdere kan købes i handelen fra forskellige kilder eller konstrueres.
The main differences between the original 2009 version and the updated 2013 version of the OECD test guideline concern, but are not limited to: the use of the BCOP test method to identify chemicals not requiring classification according to UN GHS (paragraphs 2 and 7); clarifications on the applicability of the BCOP test method to the testing of alcohols, ketones and solids (paragraphs 6 and 7) and of substances and mixtures (paragraph 8); clarifications on how surfactant substances and surfactant-containing mixtures should be tested (paragraph 28); updates and clarifications regarding the positive controls (paragraphs 39 and 40); an update of the BCOP test method decision criteria (paragraph 47); an update of the study acceptance criteria (paragraph 48); an update to the test report elements (paragraph 49); an update of Appendix 1 on definitions; the addition of Appendix 2 for the predictive capacity of the BCOP test method under various classification systems; an update of Appendix 3 on the list of proficiency chemicals; and an update of Appendix 4 on the BCOP corneal holder (paragraph 1) and on the opacitometer (paragraphs 2 and 3).It is currently generally accepted that, in the foreseeable future, no single in vitro eye irritation test will be able to replace the in vivo Draize eye test to predict across the full range of irritation for different chemical classes.
Kilde til okseøjne og deres alder samt udvælgelse af dyrearter
However, strategic combinations of several alternative test methods within a (tiered) testing strategy may be able to replace the Draize eye test (5).
Kvæg, som sendes til slagterier, aflives typisk enten med henblik på anvendelse til konsum eller anden kommerciel udnyttelse.
The Top-Down approach (5) is designed to be used when, based on existing information, a chemical is expected to have high irritancy potential, while the Bottom-Up approach (5) is designed to be used when, based on existing information, a chemical is expected not to cause sufficient eye irritation to require a classification.
Kun raske dyr, som anses for egnede til at indgå i menneskets fødekæde, anvendes som kilde til corneae til brug i BCOP-forsøgsmetoden.
The BCOP test method is an in vitro test method that can be used under certain circumstances and with specific limitations for eye hazard classification and labeling of chemicals.
Eftersom vægtintervallet for kvæg er bredt og afhænger af race, alder og køn, er der ingen anbefalet vægt for dyrene på slagtetidspunktet.
While it is not considered valid as a stand-alone replacement for the in vivo rabbit eye test, the BCOP test method is recommended as an initial step within a testing strategy such as the Top-Down approach suggested by Scott et al.
Der kan forekomme variationer i corneadimensioner ved anvendelse af øjne fra dyr med forskellig alder.
to identify chemicals inducing serious eye damage, i.e. chemicals to be classified as UN GHS Category 1, without further testing (4).
Corneae med en vandret diameter > 30,5 mm og værdier for den centrale corneatykkelse (CCT) på ≥ 1100 μm stammer i almindelighed fra kvæg, som er mere end otte år gamle, mens corneae med en vandret diameter < 28,5 mm og CCT < 900 μm i almindelighed stammer fra kvæg, som er mindre end fem år gamle (14).
The BCOP test method is also recommended to identify chemicals that do not require classification for eye irritation or serious eye damage, as defined by the UN GHS (UN GHS No Category) (4) within a testing strategy such as the Bottom-up approach (5).
Derfor anvendes der typisk ikke øjne fra kvæg, som er mere end 60 måneder gamle.
However, a chemical that is not predicted as causing serious eye damage or as not classified for eye irritation/serious eye damage with the BCOP test method would require additional testing (in vitro and/or in vivo) to establish a definitive classification.
Øjne fra kvæg, som er mindre end 12 måneder gamle, har traditionelt ikke været anvendt, eftersom disse øjne stadig er i udviklingsfasen, og corneatykkelsen og -diameteren er betydeligt mindre end det rapporterede for øjne fra voksent kvæg.
The purpose of this test method is to describe the procedures used to evaluate the eye hazard potential of a test chemical as measured by its ability to induce opacity and increased permeability in an isolated bovine cornea.
Da yderligere vurdering af betydningen af corneastørrelse eller -tykkelse for responsen på ætsende og irriterende kemikalier ville være nyttig, opfordres brugerne til at rapportere den estimerede alder og/eller vægt for de dyr, hvorfra de corneae, der undersøges, stammer.
Toxic effects to the cornea are measured by: (i) decreased light transmission (opacity), and (ii) increased passage of sodium fluorescein dye (permeability).
Indsamling og transport af øjne til laboratoriet
The opacity and permeability assessments of the cornea following exposure to a test chemical are combined to derive an In Vitro Irritancy Score (IVIS), which is used to classify the irritancy level of the test chemical.
Øjnene indsamles af slagteriarbejdere.
Definitions are provided in Appendix 1.
For at minimere mekanisk og anden beskadigelse af øjnene bør de enukleeres hurtigst muligt efter dyrenes aflivning og nedkøles straks efter enukleering og under transport.
This test method is based on the ICCVAM BCOP test method protocol (6)(7), which was originally developed from information obtained from the Institute for in vitro Sciences (IIVS) protocol and INVITTOX Protocol 124 (8).
For at forhindre at øjnene eksponeres for potentielt irriterende kemikalier, må slagteriarbejderne ikke anvende rensemiddel, når de skyller dyrenes hoveder.
The latter represents the protocol used for the European Community-sponsored prevalidation study conducted in 1997-1998.
Øjnene bør nedsænkes helt i nedkølet Hanks' Balanced Salt Solution (HBSS) i en beholder af en passende størrelse og transporteres til laboratoriet på en sådan måde, at ødelæggelse og/eller bakteriekontaminering minimeres.
Both of these protocols were based on the BCOP test method first reported by Gautheron et al.
Eftersom øjnene indsamles under slagteprocessen, vil de kunne blive eksponeret for blod og andre biologiske materialer, herunder bakterier og andre mikroorganismer.
The BCOP test method can be used to identify chemicals inducing serious eye damage as defined by UN GHS, i.e. chemicals to be classified as UN GHS Category 1 (4).
Det er derfor vigtigt at sikre, at risikoen for kontaminering minimeres (f.eks. ved at opbevare beholderen med øjnene på våd is under indsamling og transport, ved at tilsætte antibiotika til den HBSS, som øjnene opbevares i under transport [f.eks. penicillin i en koncentration på 100 IE/ml og streptomycin i en koncentration på 100 μg/ml)].
When used for this purpose, the BCOP test method has an overall accuracy of 79 % (150/191), a false positive rate of 25 % (32/126), and a false negative rate of 14 % (9/65), when compared to in vivo rabbit eye test method data classified according to the UN GHS classification system (3) (see Appendix 2, Table 1).
Tidsintervallet mellem indsamling af øjnene og anvendelsen af corneae i BCOP-forsøgsmetoden bør minimeres (typisk indsamling og anvendelse samme dag), og det bør påvises, at intervallets varighed ikke påvirker assayresultaterne negativt.
When test chemicals within certain chemical (i.e., alcohols, ketones) or physical (i.e., solids) classes are excluded from the database, the BCOP test method has an overall accuracy of 85 % (111/131), a false positive rate of 20 % (16/81), and a false negative rate of 8 % (4/50) for the UN GHS classification system (3).
Disse resultater er baseret på udvælgelseskriterierne for øjnene såvel som de positive og negative kontrolresponser.
The potential shortcomings of the BCOP test method when used to identify chemicals inducing serious eye damage (UN GHS Category 1) are based on the high false positive rates for alcohols and ketones and the high false negative rate for solids observed in the validation database (1)(2)(3).
Alle de øjne, som anvendes i assayet, bør stamme fra samme gruppe øjne, som er indsamlet på en bestemt dag.
However, since not all alcohols and ketones are over-predicted by the BCOP test method and some are correctly predicted as UN GHS Category 1, these two organic functional groups are not considered to be out of the applicability domain of the test method.
Udvælgelseskriterier for øjne, der anvendes i BCOP-forsøgsmetoden
It is up to the user of this test method to decide if a possible over-prediction of an alcohol or ketone can be accepted or if further testing should be performed in a weight-of-evidence approach.
Når øjnene er ankommet til laboratoriet, undersøges de omhyggeligt for defekter, herunder øget uklarhed, ridser og neovaskularisering.
Regarding the false negative rates for solids, it should be noted that solids may lead to variable and extreme exposure conditions in the in vivo Draize eye irritation test, which may result in irrelevant predictions of their true irritation potential (10).
Der anvendes kun corneae fra øjne, som er fri for sådanne defekter.
It should also be noted that none of the false negatives identified in the ICCVAM validation database (2)(3), in the context of identifying chemicals inducing serious eye damage (UN GHS Category 1), resulted in IVIS ≤ 3, which is the criterion used to identify a test chemical as a UN GHS No Category.
Kvaliteten af hver enkelt cornea vurderes også på senere assaytrin.
Moreover, BCOP false negatives in this context are not critical since all test chemicals that produce an 3 < IVIS ≤ 55 would be subsequently tested with other adequately validated in vitro tests, or as a last option in rabbits, depending on regulatory requirements, using a sequential testing strategy in a weight-of-evidence approach.
Corneae med en uklarhed på mere end syv uklarhedsenheder eller tilsvarende for det opacitometer og de corneaholdere, der anvendes efter en indledende ligevægtsindstillingsperiode på en time, skal kasseres (BEMÆRK: opacitometeret bør kalibreres med uklarhedsstandarder, som anvendes til at fastlægge uklarhedsenhederne, se tillæg 4).
Given the fact that some solid chemicals are correctly predicted by the BCOP test method as UN GHS Category 1, this physical state is also not considered to be out of the applicability domain of the test method.
Hver behandlingsgruppe (testkemikalie, samtidige negative og positive kontroller) består af minimum tre øjne.
Investigators could consider using this test method for all types of chemicals, whereby an IVIS > 55 should be accepted as indicative of a response inducing serious eye damage that should be classified as UN GHS Category 1 without further testing.
Der bør anvendes tre corneae som negative kontrolcorneae i BCOP-forsøgsmetoden.
However, as already mentioned, positive results obtained with alcohols or ketones should be interpreted cautiously due to potential over-prediction.
Eftersom alle corneae udskæres fra det hele øjeæble og anbringes i corneakamrene, er der risiko for håndteringsforårsagede artefakter i de individuelle værdier for cornea-uklarhed og -permeabilitet (inklusive negativ kontrol).
The BCOP test method can also be used to identify chemicals that do not require classification for eye irritation or serious eye damage under the UN GHS classification system (4).
Uklarheds- og permeabilitetsværdierne for de corneae, der fungerer som negativ kontrol, anvendes desuden til at korrigere uklarheds- og -permeabilitetsværdierne for testkemikaliebehandlede og positiv kontrol-behandlede corneae i IVIS-beregningerne.
When used for this purpose, the BCOP test method has an overall accuracy of 69 % (135/196), a false positive rate of 69 % (61/89), and a false negative rate of 0 % (0/107), when compared to in vivo rabbit eye test method data classified according to the UN GHS classification system (3) (see Appendix 2, Table 2).
Præparering af øjnene
The false positive rate obtained (in vivo UN GHS No Category chemicals producing an IVIS > 3, see paragraph 47) is considerably high, but not critical in this context since all test chemicals that produce an 3 < IVIS ≤ 55 would be subsequently tested with other adequately validated in vitro tests, or as a last option in rabbits, depending on regulatory requirements, using a sequential testing strategy in a weight-of-evidence approach.
Corneae, som er fri for defekter, fridissekeres således, at der stadig er en 2-3 mm sclerakant tilbage til hjælp ved efterfølgende håndtering, idet det tilstræbes at undgå at beskadige cornea-epitelet og -endotelet.
The BCOP test method shows no specific shortcomings for the testing of alcohols, ketones and solids when the purpose is to identify chemicals that do not require classification for eye irritation or serious eye damage (UN GHS No Category) (3).
Isolerede corneae anbringes i specialdesignede corneaholdere, der består af et forreste og bageste kammer, som grænser op til henholdsvis epitel- og endotelsiden af cornea.
Investigators could consider using this test method for all types of chemicals, whereby a negative result (IVIS ≤ 3) should be accepted as indicative that no classification is required (UN GHS No Category).
Begge kamre fyldes rigeligt op med forvarmet Eagle's Minimum Essential Medium (EMEM) fri for phenolrødt (bageste kammer først), idet det sikres, at der ikke dannes bobler.
Since the BCOP test method can only identify correctly 31 % of the chemicals that do not require classification for eye irritation or serious eye damage, this test method should not be the first choice to initiate a Bottom-Up approach (5), if other validated and accepted in vitro methods with similar high sensitivity but higher specificity are available.
Derpå bringes anordningen i ligevægt ved 32 ± 1 °C i mindst en time for at gøre det muligt for corneae at komme i ligevægt med mediet og opnå normal metabolisk aktivitet i det omfang, det er muligt (den tilnærmelsesvise temperatur af cornea-overfladen in vivo er 32 °C).
The BCOP test method is therefore considered applicable to the testing of both substances and mixtures.
Efter ligevægtsindstillingsperioden tilsættes frisk forvarmet EMEM fri for phenolrødt til begge kamre, og der aflæses basislinje-uklarhed for hver cornea.
The BCOP test method is not recommended for the identification of test chemicals that should be classified as irritating to eyes (UN GHS Category 2 or Category 2A) or test chemicals that should be classified as mildly irritating to eyes (UN GHS Category 2B) due to the considerable number of UN GHS Category 1 chemicals underclassified as UN GHS Category 2, 2A or 2B and UN GHS No Category chemicals overclassifed as UN GHS Category 2, 2A or 2B (2)(3).
Alle corneae, som viser makroskopisk vævsbeskadigelse (f.eks. ridser, pigmentering, neovaskularisering) eller en uklarhed på mere end syv uklarhedsenheder eller tilsvarende for det opacitometer og de corneaholdere, der anvendes, kasseres.
For this purpose, further testing with another suitable method may be required.
Mindst tre corneae udvælges som negative kontrolcorneae (eller opløsningsmiddelkontrolcorneae).
All procedures with bovine eyes and bovine corneas should follow the testing facility's applicable regulations and procedures for handling animal-derived materials, which include, but are not limited to, tissues and tissue fluids.
De resterende corneae fordeles derpå i en behandlingsgruppe og en positiv kontrolgruppe.
Universal laboratory precautions are recommended (11).
Eftersom varmekapaciteten for vand er højere end for luft, giver vand mere stabile temperaturbetingelser til inkubering.
Whilst the BCOP test method does not consider conjunctival and iridal injuries, it addresses corneal effects, which are the major driver of classification in vivo when considering the UN GHS classification.
Derfor anbefales det at benytte et vandbad til at holde corneaholderen og dens indhold ved 32 ± 1 °C.
The reversibility of corneal lesions cannot be evaluated per se in the BCOP test method.
Der kan dog også anvendes luftinkubatorer under forudsætning af omhyggelig opretholdelse af en stabil temperatur (f.eks. ved forvarmning af holdere og medier).
It has been proposed, based on rabbit eye studies, that an assessment of the initial depth of corneal injury may be used to identify some types of irreversible effects (12).
Påføring af testkemikaliet
However, further scientific knowledge is required to understand how irreversible effects not linked with initial high level injury occur.
Der anvendes to forskellige behandlingsprotokoller — en for væsker og overfladeaktive stoffer (faste stoffer eller væsker) og en for ikke-overfladeaktive stoffer.
Finally, the BCOP test method does not allow for an assessment of the potential for systemic toxicity associated with ocular exposure.
Væsker testes ufortyndede.
This test method will be updated periodically as new information and data are considered.
Halvfaste stoffer, cremer og vokser testes typisk som væsker.
For example, histopathology may be potentially useful when a more complete characterisation of corneal damage is needed.
Blandinger, der indeholder overfladeaktive stoffer, kan testes ufortyndet eller fortyndet til en passende koncentration, afhængigt af de relevante eksponeringsscenarier in vivo.
A laboratory can use these chemicals to demonstrate their technical competence in performing the BCOP test method prior to submitting BCOP test method data for regulatory hazard classification purposes.
Der bør gives passende begrundelse for den testede koncentration.
The BCOP test method is an organotypic model that provides short-term maintenance of normal physiological and biochemical function of the bovine cornea in vitro.
Corneae eksponeres for væsker og overfladeaktive stoffer i 10 minutter.
In this test method, damage by the test chemical is assessed by quantitative measurements of changes in corneal opacity and permeability with an opacitometer and a visible light spectrophotometer, respectively.
Anvendelse af andre eksponeringstider bør ledsages af en tilstrækkelig videnskabelig begrundelse.
Both measurements are used to calculate an IVIS, which is used to assign an in vitro irritancy hazard classification category for prediction of the in vivo ocular irritation potential of a test chemical (see Decision Criteria in paragraph 48).
Der henvises til tillæg 1 for en definition af overfladeaktive stoffer og blandinger indeholdende overfladeaktivt stof.
The BCOP test method uses isolated corneas from the eyes of freshly slaughtered cattle.
Ikke-overfladeaktive faste stoffer testes typisk som opløsninger eller opslæmninger ved en koncentration på 20 % vægt/volumen i en 0,9 % natriumchloridopløsning, destilleret vand eller et andet opløsningsmiddel, som påviseligt ikke påvirker testsystemet negativt.
Corneal opacity is measured quantitatively as the amount of light transmission through the cornea.
Under visse omstændigheder og med behørig videnskabelig begrundelse kan faste stoffer også testes i ren form ved direkte påføring på corneaoverfladen ved anvendelse af metoden med åbent kammer (jf. punkt 32).
Permeability is measured quantitatively as the amount of sodium fluorescein dye that passes across the full thickness of the cornea, as detected in the medium in the posterior chamber.
Corneae eksponeres for faste stoffer i fire timer, men som for væsker og overfladeaktive stoffer kan der anvendes alternative eksponeringstider med en tilstrækkelig videnskabelig begrundelse.
Test chemicals are applied to the epithelial surface of the cornea by addition to the anterior chamber of the corneal holder.
Der kan anvendes forskellige behandlingsmetoder alt efter testkemikaliets fysiske natur og kemiske egenskaber (f.eks. faste stoffer, væsker, viskøse kontra ikke-viskøse væsker).
Appendix 4 provides a description and a diagram of a corneal holder used in the BCOP test method.
I den forbindelse er det absolut påkrævet at sikre, at testkemikaliet dækker epiteloverfladen tilstrækkeligt, og at det fjernes tilstrækkeligt under skylletrinnene.
Corneal holders can be obtained commercially from different sources or can be constructed.
Der anvendes typisk en metode med lukket kammer for ikke-viskøse til let viskøse flydende testkemikalier, mens der typisk anvendes en metode med åbent kammer for halvviskøse og viskøse flydende testkemikalier og for rene faste stoffer.
Source and Age of Bovine Eyes and Selection of Animal Species
Ved metoden med lukket kammer indføres der tilstrækkeligt testkemikalie (750 μl) til at dække cornea-epitelsiden i det forreste kammer gennem doseringshullerne på kammerets overside, og hullerne lukkes efterfølgende med kammerpropperne under eksponeringen.
Cattle sent to slaughterhouses are typically killed either for human consumption or for other commercial uses.
Det er vigtigt at sikre, at hver cornea eksponeres for et testkemikalie i det rette tidsinterval.
Only healthy animals considered suitable for entry into the human food chain are used as a source of corneas for use in the BCOP test method.
Ved metoden med åbent kammer fjernes vindueslåseringen og glasvinduet fra det forreste kammer inden behandling.
Because cattle have a wide range of weights, depending on breed, age, and sex, there is no recommended weight for the animal at the time of slaughter.
Kontrol- eller testkemikaliet (750 μl — nok testkemikalie til at dække cornea helt) påføres direkte på cornea-epiteloverfladen ved anvendelse af en mikropipette.
Variations in corneal dimensions can result when using eyes from animals of different ages.
Hvis et testkemikalie er vanskeligt at pipettere, kan testkemikaliet fyldes i en pipette med positiv fortrængning under tryk for at lette doseringen.
Corneas with a horizontal diameter > 30,5 mm and central corneal thickness (CCT) values ≥ 1100 μm are generally obtained from cattle older than eight years, while those with a horizontal diameter < 28,5 mm and CCT < 900 μm are generally obtained from cattle less than five years old (14).
Spidsen på pipetten med positiv fortrængning indsættes i sprøjtens doseringsspids, således at materialet kan fyldes over i fortrængningsspidsen under tryk.
For this reason, eyes from cattle greater than 60 months old are not typically used.
Samtidig trykkes sprøjtestemplet ned, efterhånden som pipettestemplet trækkes opad.
Eyes from cattle less than 12 months of age have not traditionally been used since the eyes are still developing and the corneal thickness and corneal diameter are considerably smaller than that reported for eyes from adult cattle.
Hvis der dukker luftbobler op i pipettespidsen, fjernes testkemikaliet (det presses ud), og processen gentages, indtil spidsen er fyldt uden luftbobler.
However, the use of corneas from young animals (i.e., 6 to 12 months old) is permissible since there are some advantages, such as increased availability, a narrow age range, and decreased hazards related to potential worker exposure to Bovine Spongiform Encephalopathy (15).