natgillin/translations-raw huggingface dataset:
corneatykkelse ved tidspunkt t
In this test method, damage by the test chemical is assessed by determination of corneal swelling, opacity, and fluorescein retention.
corneatykkelse ved tidspunkt
While the latter two parameters involve a qualitative assessment, analysis of corneal swelling provides for a quantitative assessment.
ved tidspunkt
Each measurement is either converted into a quantitative score used to calculate an overall Irritation Index, or assigned a qualitative categorisation that is used to assign an in vitro ocular hazard classification, either as UN GHS Category 1 or as UN GHS non-classified.
Den gennemsnitlige procentvise cornea-opsvulmning for alle testøjnene beregnes for alle observationstidspunkter.
Either of these outcomes can then be used to predict the potential in vivo serious eye damage or no requirement for eye hazard classification of a test chemical (see Decision Criteria).
Ud fra den højeste gennemsnitsscore for cornea-opsvulmning som observeret på et hvilket som helst af tidspunkterne opnås der derefter en samlet kategoriscore for hvert testkemikalie (jf. punkt 51).
However, no classification can be given for chemicals not predicted as causing serious eye damage or as not classified with the ICE test method (see paragraph 11).
Vurderingen af cornea-uklarhed baseres på scoring af det område af cornea, hvor uklarheden er mest udtalt som vist i tabel 1.
Source and Age of Chicken Eyes
Den gennemsnitlige værdi for cornea-uklarhed for alle testøjnene beregnes for alle observationstidspunkter.
Historically, eyes collected from chickens obtained from a slaughterhouse where they are killed for human consumption have been used for this assay, eliminating the need for laboratory animals.
Ud fra den højeste gennemsnitsscore for cornea-uklarhed som observeret på et hvilket som helst af tidspunkterne opnås der derefter en samlet kategoriscore for hvert testkemikalie (jf. punkt 51).
Only the eyes of healthy animals considered suitable for entry into the human food chain are used.
Score for cornea-uklarhed
Although a controlled study to evaluate the optimum chicken age has not been conducted, the age and weight of the chickens used historically in this test method are that of spring chickens traditionally processed by a poultry slaughterhouse (i.e., approximately 7 weeks old, 1,5 - 2,5 kg).
uklarhed
Heads should be removed immediately after sedation of the chickens, usually by electric shock, and incision of the neck for bleeding.
Meget ubetydelig uklarhed
A local source of chickens close to the laboratory should be located so that their heads can be transferred from the slaughterhouse to the laboratory quickly enough to minimise deterioration and/or bacterial contamination.
Spredte eller diffuse områder; detaljer i iris ses tydeligt
The time interval between collection of the chicken heads and placing the eyes in the superfusion chamber following enucleation should be minimised (typically within two hours) to assure meeting assay acceptance criteria.
Let skelneligt gennemskinneligt område; detaljer i iris er en anelse utydelige
Because eyes are dissected in the laboratory, the intact heads are transported from the slaughterhouse at ambient temperature (typically between 18 °C and 25 °C) in plastic boxes humidified with tissues moistened with isotonic saline.
Stærk cornea-uklarhed; ingen specifikke detaljer i iris er synlige; pupillens størrelse kan kun lige akkurat skelnes
Selection Criteria and Number of Eyes Used in the ICE
Fuldstændig cornea-uklarhed; iris usynlig
Eyes that have high baseline fluorescein staining (i.e., > 0,5) or corneal opacity score (i.e., > 0,5) after they are enucleated are rejected.
Fluoresceinretention vurderes kun ved 30-minutters observationstidspunktet som vist i tabel 2.
Each treatment group and concurrent positive control consists of at least three eyes.
Den gennemsnitlige fluoresceinretentionsværdi for alle testøjnene beregnes herefter for 30-minutters observationstidspunktet og bruges til at opnå den samlede kategoriscore for hvert testkemikalie (jf. punkt 51).
The negative control group or the solvent control (if using a solvent other than saline) consists of at least one eye.
Score for fluoresceinretention
In the case of solid materials leading to a GHS NC outcome, a second run of three eyes is recommended to confirm or discard the negative outcome.
fluoresceinretention
The eyelids are carefully excised, taking care not to damage the cornea.
Meget ubetydelig enkeltcellefarvning
Corneal integrity is quickly assessed with a drop of 2 % (w/v) sodium fluorescein applied to the corneal surface for a few seconds, and then rinsed with isotonic saline.
Enkeltcellefarvning spredt ud over hele det behandlede område af cornea
Fluorescein-treated eyes are then examined with a slit-lamp microscope to ensure that the cornea is undamaged (i.e., fluorescein retention and corneal opacity scores ≤ 0,5).
Fokal eller sammenflydende enkeltcellefarvning med høj tæthed
If undamaged, the eye is further dissected from the skull, taking care not to damage the cornea.
Fluorescein er tilbageholdt i store sammenflydende områder af cornea
The eyeball is pulled from the orbit by holding the nictitating membrane firmly with surgical forceps, and the eye muscles are cut with a bent, blunt-tipped scissor.
Morfologiske virkninger omfatter “erosion” af cornea-epitelceller, “løsning” af epitelet, “tiltagende ruhed” af cornea-overfladen og “fastklæben” af testkemikaliet til cornea.
It is important to avoid causing corneal damage due to excessive pressure (i.e., compression artifacts).
Disse resultater kan have varierende sværhedsgrad og kan forekomme samtidig.
When the eye is removed from the orbit, a visible portion of the optic nerve should be left attached.
Klassificeringen af disse resultater er subjektiv og baseret på undersøgerens fortolkning.
Once removed from the orbit, the eye is placed on an absorbent pad and the nictitating membrane and other connective tissue are cut away.
Resultaterne for cornea-uklarhed, -opsvulmning og -fluoresceinretention bør vurderes særskilt for at finde frem til en ICE-stofgruppe for hvert endepunkt.
The enucleated eye is mounted in a stainless steel clamp with the cornea positioned vertically.
Derefter kombineres ICE-stofgrupperne for hvert endepunkt for at opnå en irritationsklassificering (Irritancy Classification) for hvert testkemikalie.
The clamp is then transferred to a chamber of the superfusion apparatus (18).
Når hvert af endepunkterne er vurderet, kan der fastlægges ICE-stofgrupper på grundlag af forudfastsatte intervaller.
The clamps should be positioned in the superfusion apparatus such that the entire cornea is supplied with the isotonic saline drip (3-4 drops per minute or 0,1 to 0,15 ml/min).
Fortolkning af cornea-opsvulmning (tabel 3), -uklarhed (tabel 4) og -fluoresceinretention (tabel 5) ved anvendelse af fire ICE-stofgrupper udføres ud fra nedenstående skalaer: Det er vigtigt at bemærke, at scorerne for cornea-opsvulmning, der vises i tabel 3, kun er relevante, hvis tykkelsen måles med et spaltelampemikroskop (f.eks. Haag-Streit BP900) med dybdemålingsanordning nr. 1 og med spaltebredden indstillet til 9 1
The chambers of the superfusion apparatus should be temperature controlled at 32 ± 1,5 °C.
, svarende til 0,095 mm.
Appendix 3 provides a diagram of a typical superfusion apparatus and the eye clamps, which can be obtained commercially or constructed.
Brugerne skal være opmærksomme på, at spaltelampemikroskoper kan give forskellige corneatykkelsesmålinger alt efter indstillingen af spaltebredden.
The apparatus can be modified to meet the needs of an individual laboratory (e.g. to accommodate a different number of eyes).
Tabel 3
After being placed in the superfusion apparatus, the eyes are again examined with a slit-lamp microscope to ensure that they have not been damaged during the dissection procedure.
ICE-klassificeringskriterier for cornea-opsvulmning
Corneal thickness should also be measured at this time at the corneal apex using the depth measuring device on the slit-lamp microscope.
Gennemsnitlig cornea-opsvulmning (%) [8]
Eyes with; (i), a fluorescein retention score of > 0,5; (ii) corneal opacity > 0,5; or, (iii), any additional signs of damage should be replaced.
ICE-stofgruppe
For eyes that are not rejected based on any of these criteria, individual eyes with a corneal thickness deviating more than 10 % from the mean value for all eyes are to be rejected.
0-5
Users should be aware that slit-lamp microscopes could yield different corneal thickness measurements if the slit-width setting is different.
> 5-12
The slit-width should be set at 0,095 mm.
> 12-18 (> 75 min. efter behandling)
Once all eyes have been examined and approved, the eyes are incubated for approximately 45 to 60 minutes to equilibrate them to the test system prior to dosing.
> 12-18 (≤ 75 min. efter behandling)
Following the equilibration period, a zero reference measurement is recorded for corneal thickness and opacity to serve as a baseline (i.e., time = 0).
18-26
The fluorescein score determined at dissection is used as the baseline measurement for that endpoint.
> 26-32 (> 75 min. efter behandling)
Immediately following the zero reference measurements, the eye (in its holder) is removed from the superfusion apparatus, placed in a horizontal position, and the test chemical is applied to the cornea.
> 26-32 (≤ 75 min. efter behandling)
Liquid test chemicals are typically tested undiluted, but may be diluted if deemed necessary (e.g. as part of the study design).
Tabel 4
The preferred solvent for diluted test chemicals is physiological saline.
ICE-klassificeringskriterier for uklarhed
However, alternative solvents may also be used under controlled conditions, but the appropriateness of solvents other than physiological saline should be demonstrated.
Maksimal gennemsnitlig uklarhedsscore [9]
Liquid test chemicals are applied to the cornea such that the entire surface of the cornea is evenly covered with the test chemical; the standard volume is 0,03 ml.
Tabel 5
If possible, solid test chemicals should be ground as finely as possible in a mortar and pestle, or comparable grinding tool.
ICE-klassificeringskriterier for gennemsnitlig fluoresceinretention
The powder is applied to the cornea such that the surface is uniformly covered with the test chemical; the standard amount is 0,03 g.
Gennemsnitlig fluoresceinretentionsscore 30 minutter efter behandling [10]
The test chemical (liquid or solid) is applied for 10 seconds and then rinsed from the eye with isotonic saline (approximately 20 ml) at ambient temperature.
In vitro-klassificeringen for et testkemikalie fastsættes ved at aflæse den GHS-klassificering, der svarer til kombinationen af kategorier opnået for cornea-opsvulmning, -uklarhed og -fluoresceinretention som beskrevet i tabel 6.
The eye (in its holder) is subsequently returned to the superfusion apparatus in the original upright position.
Tabel 6
In case of need, additional rinsing may be used after the 10-sec application and at subsequent time points (e.g. upon discovery of residues of test chemical on the cornea).
Overordnede in vitro-klassificeringer
In general the amount of saline additionally used for rinsing is not critical, but the observation of adherence of chemical to the cornea is important.
UN GHS-klassificering
Concurrent negative or solvent/vehicle controls and positive controls should be included in each experiment.
Kombinationer af de tre endepunkter
When testing liquids at 100 % or solids, physiological saline is used as the concurrent negative control in the ICE test method to detect non-specific changes in the test system, and to ensure that the assay conditions do not inappropriately result in an irritant response.
Andre kombinationer
When testing diluted liquids, a concurrent solvent/vehicle control group is included in the test method to detect non-specific changes in the test system, and to ensure that the assay conditions do not inappropriately result in an irritant response.
2 × IV, 1 × II [11]2 × IV, 1 × I [11]Cornea-uklarhed ≥ 3 efter 30 min. (for mindst to øjne)
As stated in paragraph 31, only a solvent/vehicle that has been demonstrated to have no adverse effects on the test system can be used.
Cornea-uklarhed = 4 på et hvilket som helst tidspunkt (for mindst to øjne)
A known ocular irritant is included as a concurrent positive control in each experiment to verify that an appropriate response is induced.
Markant løsning af epitelet (for mindst et øje)
As the ICE assay is being used in this test method to identify corrosive or severe irritants, the positive control should be a reference chemical that induces a severe response in this test method.
En test anses for acceptabel, hvis de samtidige negative kontroller eller opløsningsmiddel-/bærestofkontroller og de samtidige positive kontroller er identificeret som henholdsvis GHS uden for kategori og GHS-kategori 1.
However, to ensure that variability in the positive control response across time can be assessed, the magnitude of the severe response should not be excessive.
CAS-registreringsnummeret (RN), hvis det kendes
Examples of positive controls for liquid test chemicals are 10 % acetic acid or 5 % benzalkonium chloride, while examples of positive controls for solid test chemicals are sodium hydroxide or imidazole.
renhed og sammensætning af test-/kontrolkemikalier (i vægtprocent) i det omfang, disse oplysninger er tilgængelige
Treated corneas are evaluated prior to treatment and at 30, 75, 120, 180, and 240 minutes (± 5 minutes) after the post-treatment rinse.
fysisk-kemiske egenskaber, såsom fysisk tilstand, flygtighed, pH, stabilitet, kemikaliegruppe og vandopløselighed, som er relevante for undersøgelsens gennemførelse
These time points provide an adequate number of measurements over the four-hour treatment period, while leaving sufficient time between measurements for the requisite observations to be made for all eyes.
eventuel behandling af test-/kontrolkemikalier inden testen (f.eks. opvarmning, formaling)
The endpoints evaluated are corneal opacity, swelling, fluorescein retention, and morphological effects (e.g. pitting or loosening of the epithelium).
stabilitet, hvis den kendes.
All of the endpoints, with the exception of fluorescein retention (which is determined only prior to treatment and 30 minutes after test chemical exposure) are determined at each of the above time points.
navn og adresse på sponsoren, testfaciliteten og undersøgelseslederen
Photographs are advisable to document corneal opacity, fluorescein retention, morphological effects and, if conducted, histopathology.
identifikation af kilden til øjnene (f.eks. den facilitet, hvor de er indsamlet).
After the final examination at four hours, users are encouraged to preserve eyes in an appropriate fixative (e.g. neutral buffered formalin) for possible histopathological examination (see paragraph 14 and reference (8) for details).
beskrivelse af det anvendte testsystem
Corneal swelling is determined from corneal thickness measurements made with an optical pachymeter on a slit-lamp microscope.
det anvendte spaltelampemikroskop (f.eks. model) og instrumentindstillinger for det anvendte spaltelampemikroskop
It is expressed as a percentage and is calculated from corneal thickness measurements according to the following formula:
reference til historiske negative og positive kontrolresultater og, hvis det er relevant, historiske data, der viser acceptable samtidige referencekontrolintervaller
corneal thickness at time t
procedure, som anvendes til at sikre integriteten (dvs. nøjagtighed og pålidelighed) af forsøgsmetoden over tid (f.eks. periodisk test af kompetencekemikalier).
corneal thickness at time
donordyrenes alder og vægt og, hvis de er tilgængelige, andre særlige karakteristika ved de dyr, som øjnene er indsamlet fra (f.eks. køn, stamme)
thickness at time
opbevarings- og transportbetingelser for øjnene (f.eks. dato og klokkeslæt for øjenindsamling, tidsinterval mellem indsamling af kyllingehovederne og anbringelse af enukleerede øjne i superfusionsapparatets kammer)
The mean percentage of corneal swelling for all test eyes is calculated for all observation time points.
præparering og montering af øjne, herunder specifikation af deres kvalitet, øjenkamrenes temperatur og kriterierne for udvælgelse af øjne, der anvendes til test.
Based on the highest mean score for corneal swelling, as observed at any time point, an overall category score is then given for each test chemical (see paragraph 51).
dosis af testkemikalie, indgivelse og eksponeringstid
Corneal opacity is evaluated by using the area of the cornea that is most densely opacified for scoring as shown in Table 1.
observationstidspunkter (før og efter behandling)
The mean corneal opacity value for all test eyes is calculated for all observation time points.
beskrivelse af eventuelle ændringer i testproceduren.
Based on the highest mean score for corneal opacity, as observed at any time point, an overall category score is then given for each test chemical (see paragraph 51).
opstilling i tabelform af de opnåede scorer for cornea-opsvulmning, -uklarhed og fluoresceinretention for hvert enkelt øje og på hvert observationstidspunkt, herunder den gennemsnitlige score for hvert observationstidspunkt for alle undersøgte øjne
Corneal opacity scores
de højeste gennemsnitlige scorer for konstateret cornea-opsvulmning, -uklarhed og fluoresceinretention (fra et hvilket som helst tidspunkt) og den tilhørende ICE-klasse.
Score
Beskrivelse af eventuelle andre observationer
Observation
den afledte in vitro GHS-klassificering
opacity
fotografier af øjnene, hvis det er relevant.
Very faint opacity
Tilgængelig på: [http://ecvam.jrc.it/index.htm].
Scattered or diffuse areas; details of the iris are clearly visible
Tilgængelig på: [http://www.unece.org/trans/danger/publi/ghs/ghs_rev04/04files_e.html].
Easily discernible translucent area; details of the iris are slightly obscured
Series on Testing and Assessment, No.160, OECD, Paris.
Severe corneal opacity; no specific details of the iris are visible; size of the pupil is barely discernible
Tilgængelig på: [http://iccvam.niehs.nih.gov/methods/ocutox/ivocutox/ocu_brd_ice.htm]
Complete corneal opacity; iris invisible
Tilgængelig på: [http://ecvam-dbalm.jrc.ec.europa.eu/].
Fluorescein retention is evaluated at the 30 minute observation time point only as shown in Table 2.
Tilgængelig på: [http://www.cdc.gov/ncidod/dhqp/pdf/isolation2007.pdf].
The mean fluorescein retention value of all test eyes is then calculated for the 30-minute observation time point, and used for the overall category score given for each test chemical (see paragraph 51).
Et benchmarkkemikalie bør have følgende egenskaber: i) en eller flere ensartede og pålidelige kilder), ii) strukturel og funktionel lighed med den klasse af kemikalier, der testes, iii) kendte fysisk-kemiske egenskaber, iv) støttedata om kendte virkninger og v) kendt styrke i det ønskede responsområde
Fluorescein retention scores
Cornea-opsvulmning
fluorescein retention
Objektiv måling i ICE-testen af graden af cornea-udvidelse efter eksponering for et testkemikalie.
Very minor single cell staining
Den udtrykkes som en procentdel og beregnes ud fra basismålinger af cornea-tykkelsen (inden dosis) og tykkelsen, der registreres med regelmæssige intervaller efter eksponering for testkemikaliet i ICE-testen.
Single cell staining scattered throughout the treated area of the cornea
Graden af cornea-opsvulmning er indikativ for beskadigelse af cornea.
Focal or confluent dense single cell staining
Øjenirritation
Confluent large areas of the cornea retaining fluorescein
Frembringelse af forandringer i øjet, som opstår efter påføring af testkemikaliet på øjets anteriore overflade, og som er fuldt reversible inden for 21 dage efter påføring.
Morphological effects include “pitting” of corneal epithelial cells, “loosening” of epithelium, “roughening” of the corneal surface and “sticking” of the test chemical to the cornea.
Udskiftelige med »Reversible virkninger på øjet« og »UN GHS-kategori 2« (4).
These findings can vary in severity and may occur simultaneously.
Fluoresceinretention
The classification of these findings is subjective according to the interpretation of the investigator.
Subjektiv måling i ICE-testen af det omfang, hvori natriumfluorescein tilbageholdes af epitelceller i cornea efter eksponering for et teststof.
Results from corneal opacity, swelling, and fluorescein retention should be evaluated separately to generate an ICE class for each endpoint.
Graden af fluoresceinretention er indikativ for beskadigelse af cornea-epitelet.
The ICE classes for each endpoint are then combined to generate an Irritancy Classification for each test chemical.
se »Alvorlig øjenskade« og »UN GHS-kategori 1«.
Once each endpoint has been evaluated, ICE classes can be assigned based on a predetermined range.
Stoffer, der ikke er klassificeret som øjenirriterende (UN GHS-kategori 2) eller som forårsagende alvorlig øjenskade (UN GHS-kategori 1).
Interpretation of corneal swelling (Table 3), opacity (Table 4), and fluorescein retention (Table 5) using four ICE classes is done according to the scales shown below.
For at sikre, at det er muligt at vurdere variabiliteten i den positive kontrolrespons over tid, bør den svære respons ikke være overdrevent stor.
It is important to note that the corneal swelling scores shown in Table 3 are only applicable if thickness is measured with a slit-lamp microscope (for example Haag-Streit BP900) with depth-measuring device no.
Reversible virkninger på øjet
1 and slit-width setting at 91
se »Øjenirritation« og »UN GHS-kategori 2«.
, equalling 0,095 mm.
Spaltelampemikroskop
Users should be aware that slit-lamp microscopes could yield different corneal thickness measurements if the slit-width setting is different.
Instrument, som anvendes til direkte undersøgelse af øjet under forstørrelse tilvejebragt af et binokulært mikroskop ved frembringelse af et stereoskopisk, retvendt billede.
Table 3
Ved ICE-forsøgsmetoden anvendes dette instrument til at se kyllingeøjets anteriore strukturer samt til at foretage objektive målinger af corneas tykkelse ved at påmontere en anordning til dybdemåling.
ICE classification criteria for corneal swelling
Ethvert stof eller enhver blanding, der testes ved hjælp af denne forsøgsmetode.
Mean Corneal Swelling (%) [8]
se »Alvorlig øjenskade« og/eller »Irreversible virkninger på øjet«.
ICE Class
se »Øjenirritation« og/eller »Reversible virkninger på øjet«.
0 to 5
Stoffer, der ikke opfylder kravene med hensyn til klassificering som UN GHS-kategori 1 eller 2 (2A eller 2B).
> 5 to 12
Udskiftelig med »Ikke-klassificeret«.
> 12 to 18 (> 75 min after treatment)
Proces, hvor styrkerne og svaghederne ved forskellige oplysninger afvejes for at nå frem til og underbygge en konklusion om et stofs farepotentiale.
> 12 to 18 (≤ 75 min after treatment)
KOMPETENCEKEMIKALIER TIL ICE-FORSØGSMETODEN
> 18 to 26
Inden laboratorier påbegynder rutinemæssig brug af en forsøgsmetode, der følger denne forsøgsmetode, bør de godtgøre deres tekniske kompetence ved korrekt identifikation af øjenrisikoklassificeringen for de 13 anbefalede kemikalier i tabel 1.
> 26 to 32 (> 75 min after treatment)
Disse kemikalier er udvalgt således, at de repræsenterer responsområdet for øjenrisiko, der er baseret på resultater fra in vivo-kaninøjentesten (TG 405) og FN's GHS-klassificeringssystem (dvs. UN GHS-kategori 1, 2A, 2B eller uden for kategori) (4) (6).
> 26 to 32 (≤ 75 min after treatment)
Andre udvælgelseskriterier var, at kemikalierne er kommercielt tilgængelige, at der findes tilgængelige in vivo-referencedata af høj kvalitet, og at der findes data af høj kvalitet for ICE in vitro-metoden.
Table 4
Referencedata findes i SSD (5) og i ICCVAM Background Review Documents for ICEBCOP-forsøgsmetoden og for isoleret kyllingeøje-forsøgsmetoden (ICE [Isolated Chicken Eye]-forsøgsmetoden) (9).
ICE classification criteria for opacity
Anbefalede kemikalier til godtgørelse af teknisk kompetence i anvendelse af ICE
Maximum Mean Opacity Score [9]
In vitro-klassificering [3]
Table 5
Dibenzoyl-L-vinsyre
ICE classification criteria for mean fluorescein retention
Carboxylsyre
Mean Fluorescein Retention Score at 30 minutes post-treatment [10]