natgillin/translations-raw huggingface dataset:
stoffets eller præparatets renhed og sammensætning (i procentdele efter vægt)
purity and composition of the substance or preparation (in percentage(s) by weight),
fysiske-kemiske egenskaber, f.eks. fysisk tilstand, pH, stabilitet og opløselighed i vand, som er relevante for undersøgelsen
physico-chemical properties such as physical state, pH, stability, water solubility relevant to the conduct of the study,
Begrundelse for valg af hudmodel og forsøgsprotokol.
Justification of the skin model and protocol used.
anvendt cellesystem
cell system used,
kalibreringsinformationer for udstyr anvendt til måling af cellelevedygtighed (f.eks. spektrofotometer)
calibration information for measuring device used for measuring cell viability (e.g. Spectrophotometer),
komplet dokumentation for den anvendte hudmodel, herunder godkendelsen heraf
complete supporting information for the specific skin model used including its validity,
detaljer om den anvendte testprocedure
details of the test procedure used,
anvendte testdoser
test doses used,
beskrivelse af eventuelle ændringer i testproceduren
description of any modifications of the test procedure,
reference til historiske data for modellen
reference to historical data of the model,
angivelse i tabelform af data fra hver enkelt testprøve
tabulation of data from individual test samples,
beskrivelse af andre observerede virkninger.
description of other effects observed.
Konklusion
Conclusion.
The report recommendations of ECVAM Workshop 6 ATLA 23, 219-255.
The report recommendations of ECVAM Workshop 6 ATLA 23, p. 219-255.
In Vitro 12, 471-482.
Toxicology In Vitro 12, p. 471-482.
ICCVAM (Interagency Coordinating Committee on the Validation of Alternative Methods). (1997). Validation and Regulatory Acceptance of Toxicological Test Methods.
ICCVAM (Interagency Coordinating Committee on the Validation of Alternative Methods)., (1997) Validation and Regulatory Acceptance of Toxicological Test Methods.
Liebsch, M., Traue, D., Barrabas, C, Spielmann, H., Uphill, P., Wilkins, S., McPherson, J.P., Wiemann, C, Kaufmann, T., Remmele, M. and Holzhutter, H.G. (2000). The ECVAM prevalidation study on the use of EpiDerm for skin Corrosivity testing.
Liebsch, M., Traue, D., Barrabas, C., Spielmann, H., Uphill, P., Wilkins, S., McPherson, J.P., Wiemann, C., Kaufmann, T., Remmele, M. and Holzhutter, H.G., (2000) The ECVAM prevalidation study on the use of EpiDerm for skin Corrosivity testing.
ATLA 28, pp. 371-401.
ATLA 28, p. 371-401.
ATLA 26, 275-280.
ATLA 26, p. 275-280.
ATLA 28, 365-67.
ATLA 28, p. 365-67.
In Vitro 8, 889-891.
Toxicology In Vitro 8, p. 889-891.
Tinois E., Gaetani Q., Gayraud B., Dupont D., Rougier A., Pouradier D.X. (1994).
Tinois, E., Gaetani, Q., Gayraud, B., Dupont, D., Rougier, A., Pouradier, D.X., (1994) The Episkin model: Successful reconstruction of human epidermis in vitro.
Edited by A Rougier, AM Goldberg and HI Maibach: 133-140.
Edited by A Rougier, AM Goldberg and HI Maibach, p. 133-140
Tinois E., Tiollier J., Gaucherand M., Dumas H., Tardy M., Thivolet J. (1991).
Tinois E, Tiollier J, Gaucherand M, Dumas H, Tardy M, Thivolet J (1991).
In vitro and post -transplantation differentiation of humankeratinocytes grown on the human type IV collagen film of a bilayereddermal substitute.
In vitro and post–transplantation differentiation of human keratinocytes grown on the human type IV collagen film of a bilayered dermal substitute.
Experimental Cell Research 193: 310-319.
Experimental Cell Research 193, p. 310-319
Parentau, N.L., Bilbo, P., Molte, C.J., Mason, V.S., and Rosenberg, H.(1992). The organotypic culture of human skin keratinocytes and fibroblasts to achieve form and function.
Parentau, N.L., Bilbo, P., Molte, C.J., Mason, V.S., and Rosenberg, H., (1992) The organotypic culture of human skin keratinocytes and fibroblasts to achieve form and function.
Cytotechnology 9, 163-171.
Cytotechnology 9, p. 163-171.
Biotechnology and Bioengineering 43/8, 747-756.
Biotechnology and Bioengineering 43/8, p. 747-756.
Growth Regulation 5, 69-84.
Growth Regulation 5, p. 69-84.
Fentem, J.H., Briggs, D., Chesne', C, Elliot, G.R., Harbell, J.W., Heylings, J.R., Portes, P., Rouget, R., and van de Sandt, J.J.M., and Botham, P.A. (2001). A prevalidation study on in vitro tests for acute skin irritation: results and evaluation by the Management Team. Toxic.
Fentem, J.H., Briggs, D., Chesne’, C., Elliot, G.R., Harbell, J.W., Heylings, J.R., Portes, P., Rouget, R., and van de Sandt, J.J.M., and Botham, P.A., (2001) A prevalidation study on in vitro tests for acute skin irritation: results and evaluation by the Management Team.
In VItro 15, 57-93.
Toxicology In Vitro 15, p. 57-93.
Denne metode er ækvivalent med OECD TG 432 (2004).
This method is equivalent to OECD TG 432 (2004).
Fototoksicitet defineres som det toksiske respons på et stof, der påføres kroppen, og som enten er blevet fremkaldt af eller forstærket af (kan konstateres ved lavere doser) eksponering for lys, eller som er forårsaget af bestråling af huden efter systemisk indgift af et stof.
Phototoxicity is defined as a toxic response from a substance applied to the body which is either elicited or increased (apparent at lower dose levels) after subsequent exposure to light, or that is induced by skin irradiation after systemic administration of a substance.
In vitro 3T3 NRU-fototoksicitetstesten anvendes til at afdække det fototoksiske potentiale i et testmateriale, når det exciteres ved lyspåvirkning.
The in vitro 3T3 NRU phototoxicity test is used to identify the phototoxic potential of a test substance induced by the excited chemical after exposure to light.
Testen evaluerer fotocytotoksicitet ud fra den relative reduktion i levedygtigheden af de celler, der udsættes for det kemiske stof under lyspåvirkning, sammenlignet med samme situation uden lys.
The test evaluates photo-cytotoxicity by the relative reduction in viability of cells exposed to the chemical in the presence versus absence of light.
De stoffer, som identificeres ved denne test, er sandsynligvis fototoksiske in vivo efter systemisk påføring og fordeling på huden eller efter lokal påføring.
Substances identified by this test are likely to be phototoxic in vivo following systemic application and distribution to the skin, or after topical application.
Der er rapporteret om mange typer kemiske stoffer, der fremkalder fototoksiske virkninger (1)(2)(3)(4).
Many types of chemicals have been reported to induce phototoxic effects (1)(2)(3)(4).
Et fælles træk er deres evne til at absorbere lysenergi inden for sollysets spektrum.
Their common feature is their ability to absorb light energy within the sunlight range.
Ifølge fotokemiens grundlov (Grotthaus-Draper-loven) forudsætter fotoreaktion en tilstrækkelig optaget lysmængde.
According to the first law of photochemistry (Grotthaus-Draper Law), photoreaction requires sufficient absorption of light quanta.
Derfor skal man, inden man overvejer en biologisk testning, bestemme testkemikaliets absorptionsspektrum for UV/synligt lys i henhold til OECD Test Guideline 101.
Thus, before biological testing is considered, a UV/vis absorption spectrum of the test chemical must be determined according to OECD Test Guideline 101.
Det er påstået, at det kemiske stof sandsynligvis ikke er fotoreaktivt, hvis den molære ekstinktions- og absorptionskoefficient er mindre end 10 liter × mol-1 × cm-1.
It has been suggested that if the molar extinction/absorption coefficient is less than 10 litre × mol-1 × cm-1 the chemical is unlikely to be photoreactive.
Et kemisk stof af denne type behøver ikke nødvendigvis at blive testet i in vitro 3T3 NRU-fototoksicitetstesten eller i nogen anden biologisk test for skadelige fotokemiske virkninger (1)(5).
Such chemical may not need to be tested in the in vitro 3T3 NRU phototoxicity test or any other biological test for adverse photochemical effects (1)(5).
Se også bilag 1.
See also Appendix 1.
Pålideligheden og relevansen af in vitro 3T3 NRU-fototoksicitetstesten er blevet evalueret for nylig (6)(7)(8)(9).
The reliability and relevance of the in vitro 3T3 NRU phototoxicity test was recently evaluated (6)(7)(8) (9).
In vitro 3T3 NRU-fototoksicitetstesten har vist sig at kunne forudsige akutte fototoksicitetsvirkninger på dyr og mennesker in vivo.
The in vitro 3T3 NRU phototoxicity test was shown to be predictive of acute phototoxicity effects in animals and humans in vivo.
Testen er ikke beregnet til at forudsige andre skadelige virkninger, der måtte opstå fra samtidig påvirkning fra et kemisk stof og lys. Eksempelvis påviser den ikke fotogenotoksicitet, fotoallergi eller fotocarcinogenicitet, og den er heller ikke beregnet til vurdering af fototoksisk styrke.
The test is not designed to predict other adverse effects that may arise from combined action of a chemical and light, e.g. it does not address photogenotoxicity, photoallergy, or photocarcinogenicity, nor does it allow an assessment of phototoxic potency.
Testen er endvidere ikke beregnet til at påvise indirekte mekanismer ved fototoksicitet, virkninger af stofskifteprodukter på testmaterialet eller virkninger af blandinger.
In addition, the test has not been designed to address indirect mechanisms of phototoxicity, effects of metabolites of the test substance, or effects of mixtures.
Hvor anvendelsen af metaboliserende systemer er et generelt krav til alle in vitro-testninger til forudsigelse af genotoksisk og carcinogent potentiale, er der indtil nu i forbindelse med fototoksikologi kun få tilfælde, hvor der kræves metabolisk transformation for at få det kemiske stof til at reagere som fototoksin in vivo eller in vitro.
Whereas the use of metabolising systems is a general requirement for all in vitro tests for the prediction of genotoxic and carcinogenic potential, up to now, in the case of phototoxicology, there are only rare examples where metabolic transformation is needed for the chemical to act as a phototoxin in vivo or in vitro.
Det anses derfor hverken som nødvendigt eller videnskabeligt begrundet at gennemføre nærværende testning med et metabolisk aktiverings system.
Thus, it is neither considered necessary nor scientifically justified for the present test to be performed with a metabolic activation system.
Strålingsintensitet: intensiteten af ultraviolet (UV) eller synligt lys, der falder på en overflade. Intensiteten måles i W/m2 eller mW/cm2.
Irradiance: the intensity of ultraviolet (UV) or visible light incident on a surface, measured in W/m2 or mW/cm2.
Lysdosis: mængden (= intensitet × tid) af ultraviolet (UV) eller synligt lys, der falder på en overflade, udtrykt i joule (= W × s) pr. overfladeareal, f.eks. J/m2 eller J/cm2.
Dose of light: the quantity (= intensity × time) of ultraviolet (UV) or visible radiation incident on a surface, expressed in Joules (= W × s) per surface area, e.g. J/m2 or J/cm2.
UV-lys, bølgelængdeområder: følgende betegnelser er anbefalet af CIE (Den Internationale Belysningskommission): UVA (315-400 nm), UVB (280-315 nm) og UVC (100-280 nm). Der anvendes også andre betegnelser.
UV light wavebands: the designations recommended by the CIE (Commission Internationale de L'Eclairage) are: UVA (315-400 nm), UVB (280-315 nm) and UVC (100-280 nm).
Grænsen mellem UVB og UVA sættes ofte ved 320 nm, og UVA kan inddeles i UV-A1 og UV-A2, hvor grænsen ligger ved ca. 340 nm.
Other designations are also used; the division between UVB and UVA is often placed at 320 nm, and the UVA may be divided into UV-A1 and UV-A2 with a division made at about 340 nm.
Cellernes levedygtighed: parameter, der måler den samlede aktivitet i en cellepopulation (f.eks. optagelse af det livsvigtige farvestof Neutral Red i cellelysosomer), hvilket, afhængigt af det målte endepunkt og det anvendte testdesign, korrelerer med det samlede celleantal og/eller cellevitaliteten.
Cell viability: parameter measuring total activity of a cell population (e.g. uptake of the vital dye Neutral Red into cellular lysosomes), which, depending on the endpoint measured and the test design used, correlates with the total number and/or vitality of the cells.
Relativ cellelevedygtighed: cellelevedygtighed udtrykt i forhold til negative kontroller (opløsningsmiddel), der har været gennem hele testforløbet (enten +Irr eller –Irr), og som ikke er behandlet med kemiske teststoffer.
Relative cell viability: cell viability expressed in relation of solvent (negative) controls which have been taken through the whole test procedure (either +Irr or -Irr) but not treated with test chemical.
PIF (fotoirritationsfaktor): faktor, der beregnes ved sammenligning mellem to lige effektive cytotoksiske koncentrationer (IC50) af det kemiske teststof ved fravær af (–Irr) og ved tilstedeværelse af (+Irr) i en ikke-cytotoksisk bestråling med UVA/synligt lys.
PIF (Photo-Irritation-Factor): factor generated by comparing two equally effective cytotoxic concentrations (IC50) of the test chemical obtained in the absence (-Irr) and in the presence (+Irr) of a non-cytotoxic irradiation with UVA/vis light.
IC50: koncentrationen af det kemiske teststof, der reducerer cellelevedygtigheden med 50 %.
the concentration of the test chemical by which the cell viability is reduced by 50 %.
MPE (gennemsnitlig lyseffekt): måling, der er afledt af en matematisk analyse af de koncentrationsresponskurver, der fremkommer ved fravær af (–Irr) og ved tilstedeværelse af (+Irr) i en ikke-cytotoksisk bestråling med UVA/synligt lys.
MPE (Mean-Photo-Effect): measurement derived from mathematical analysis of the concentration response curves obtained in the absence (-Irr) and in the presence (+Irr) of a non-cytotoxic irradiation with UVA/vis light.
Fototoksicitet: akut toksisk respons, der fremkommer efter den første eksponering af huden for visse kemiske stoffer og efterfølgende eksponering for lys, eller som er fremkaldt på samme måde ved hudbestråling efter systemisk indgift af et kemisk stof.
Phototoxicity: acute toxic response that is elicited after the first exposure of skin to certain chemicals and subsequent exposure to light, or that is induced similarly by skin irradiation after systemic administration of a chemical.
In vitro 3T3 NRU-fototoksicitetstesten er baseret på en sammenligning mellem cytotoksiciteten af et kemisk stof, når det afprøves med og uden eksponering for en ikke-cytotoksisk dosis af simuleret sollys.
The in vitro 3T3 NRU phototoxicity test is based on a comparison of the cytotoxicity of a chemical when tested in the presence and in the absence of exposure to a non-cytotoxic dose of simulated solar light.
Cytotoksicitet er i denne testning udtrykt som en koncentrationsafhængig reduktion af optagelsen af det livsvigtige farvestof Neutral Red som målt 24 timer efter behandling med det kemiske teststof og bestråling (10).
Cytotoxicity in this test is expressed as a concentration-dependent reduction of the uptake of the vital dye Neutral Red when measured 24 hours after treatment with the test chemical and irradiation (10).
NR er et svagt kationisk farvestof, der let gennemtrænger cellemembraner ved ikke-diffusion og akkumuleres intracellulært i lysosomer.
NR is a weak cationic dye that readily penetrates cell membranes by non-diffusion, accumulating intracellulary in lysosomes.
Forandringer i overfladen i den sensitive lysosommembran fører til lysosomal ustabilitet og andre forandringer, der gradvist bliver uoprettelige.
Alterations of the surface of the sensitive lysosomal membrane lead to lysosomal fragility and other changes that gradually become irreversible.
Den type forandringer, der forårsages af miljøfremmede stoffer, medfører et fald i optagelsen og bindingen af NR. Det er således muligt at skelne mellem levedygtige, beskadigede og døde celler, hvilket er grundlaget for denne test.
Such changes brought about by the action of xenobiotics result in a decreased uptake and binding of NR. It is thus possible to distinguish between viable, damaged or dead cells, which is the basis of this test.
Balb/c 3T3-celler dyrkes i 24 timer, så der dannes encellede lag.
Balb/c 3T3 cells are maintained in culture for 24 h for formation of monolayers.
To 96-huls plader for hvert kemisk teststof præinkuberes med otte forskellige koncentrationer af teststoffet i 1 time. Derefter eksponeres den ene af de to plader for den højeste ikke-cytotoksiske strålingsdose, mens den anden plade holdes i mørke.
Two 96-well plates per test chemical are pre-incubated with eight different concentrations of the test substance for 1 h. Thereafter one of the two plates is exposed to the highest non-cytotoxic irradiation dose whereas the other plate is kept in the dark.
På begge plader erstattes behandlingsmediet derefter af kulturmedium, og efter endnu 24 timers inkubation bestemmes cellelevedygtigheden ved Neutral Red-optagelsen.
In both plates the treatment medium is then replaced by culture medium and after another 24 h of incubation cell viability is determined by Neutral Red uptake.
Cellelevedygtigheden udtrykkes som en procentdel i forhold til ubehandlede kontrolkulturer med opløsningsmiddel og beregnes for hver testkoncentration.
Cell viability is expressed as percentage of untreated solvent controls and is calculated for each test concentration.
For at forudsige det fototoksiske potentiale sammenholdes koncentrationerne for samme respons med og uden stråling, sædvanligvis på IC50-niveau, dvs. den koncentration, der reducerer cellelevedygtigheden til 50 % sammenlignet med de ubehandlede kontroller.
To predict the phototoxic potential, the concentration responses obtained in the presence and in the absence of irradiation are compared, usually at the IC50 level, i.e., the concentration reducing cell viability to 50 % compared to the untreated controls.
I valideringsundersøgelserne blev der anvendt en permanent muse-fibroblast cellelinje, Balb/c 3T3, klon 31, enten fra American Type Culture Collection (ATCC), Manassas, VA, USA, eller fra European Collection of Cell Cultures (ECACC), Salisbury, Wiltshire, Det Forenede Kongerige, og det anbefales derfor at anskaffe materiale fra en velanskrevet cellebank.
A permanent mouse fibroblast cell line, Balb/c 3T3, clone 31, either from the American Type Culture Collection (ATCC), Manassas, VA, USA, or from the European Collection of Cell Cultures (ECACC), Salisbury, Wiltshire, UK, was used in the validation study, and therefore is recommended to obtain from a well qualified cell depository.
Hvis der blot kan påvises ækvivalens, kan der anvendes andre celler eller cellelinjer til samme testprocedure, hvis kulturforholdene er tilpasset cellernes specifikke behov.
Other cells or cell lines may be used with the same test procedure if culture conditions are adapted to the specific needs of the cells, but equivalency must be demonstrated.
For Balb/c 3T3-celler er de korrekte forhold f.eks. DMEM (Dulbecco's Modified Eagle's Medium) suppleret med 10 % serum fra nyfødte kalve, 4 mM glutamin, penicillin (100 IU), streptomycin (100 g/ml) og inkubation i fugtig atmosfære ved 37 oC, 5-7,5 % CO2, afhængigt af buffer (se punkt 1.4.1.4, andet afsnit).
Appropriate culture media and incubation conditions should be used for routine cell passage and during the test procedure, e.g. for Balb/c 3T3 cells these are DMEM (Dulbecco's Modified Eagle's Medium) supplemented with 10 % new-born calf serum, 4 mM glutamine, penicillin (100 IU), and streptomycin (100 μg/mL), and humidified incubation at 37 oC, 5-7,5 % CO2 depending on the buffer (See Section 1.4.1.4, second paragraph.).
Der er især vigtigt, at dyrkningsforholdene for cellekulturen tillader en cellecyklustid inden for cellernes eller cellelinjernes normale historiske område.
It is particularly important that cell culture conditions assure a cell cycle time within the normal historical range of the cells or cell line used.
Celler fra nedfrosne kulturer podes i kulturmedier ved passende tæthed og dyrkes i subkultur mindst en gang, inden de anvendes i in vitro 3T3 NRU-fototoksicitetstesten.
Cells from frozen stock cultures are seeded in culture medium at an appropriate density and subcultured at least once before they are used in the in vitro 3T3 NRU phototoxicity test.
Celler, der anvendes til fototoksicitetstesten, podes i et kulturmedium med passende tæthed, så kulturerne ikke løber sammen ved testens afslutning, dvs. cellelevedygtigheden bestemmes 48 timer efter podning af cellerne.
Cells used for the phototoxicity test are seeded in culture medium at the appropriate density so that cultures will not reach confluence by the end of the test, i.e., when cell viability is determined 48 h after seeding of the cells.
For Balb/c 3T3-celler, der dyrkes på 96-huls plader, er den anbefalede podningstæthed for cellerne 1 × 104 celler pr. hul.
For Balb/c 3T3 cells grown in 96-well plates, the recommended cell seeding density is 1 × 104 cells per well.
For hver test podes kemikalieceller ensartet i to separate 96-huls plader, der begge sideløbende gennemfører hele testproceduren under identiske kulturforhold med undtagelse af den tid, hvor den ene af pladerne bestråles (+Irr), og den anden holdes i mørke (–Irr).
For each test chemical cells are seeded identically in two separate 96-well plates, which are then taken concurrently through the entire test procedure under identical culture conditions except for the time period where one of the plates is irradiated (+Irr) and the other one is kept in the dark (-Irr).
Forberedelse af teststof
Preparation of test substance
Teststoffer skal være friske og forberedes umiddelbart inden brug, medmindre data påviser, at de er stabile ved opbevaring.
Test substances must be prepared fresh, immediately prior to use unless data demonstrate their stability in storage.
Det anbefales, at enhver form for kemisk håndtering og den indledende behandling af cellerne udføres under lysforhold, der udelukker fotoaktivering eller nedbrydning af teststoffet inden bestråling.
It is recommended that all chemical handling and the initial treatment of cells be performed under light conditions that would avoid photoactivation or degradation of the test substance prior to irradiation.
Testkemikalierne skal være opløst i buffer-saltopløsninger, f.eks. Earle's Balanced Salt Solution (EBSS), eller andre fysiologiske buffer-opløsninger, der skal være fri for proteinkomponenter og lysabsorberende komponenter (f.eks. pH-indikatorfarver og vitaminer) for at undgå interferens under bestråling.
Test chemicals shall be dissolved in buffered salt solutions, e.g. Earle's Balanced Salt Solution (EBSS), or other physiologically balanced buffer solutions, which must be free from protein components, light absorbing components (e.g. pH-indicator colours and vitamins) to avoid interference during irradiation.
Da celler under bestråling holdes uden for CO2-inkubatoren i ca. 50 minutter, skal man være særligt påpasselig for at undgå alkalisering.
Since during irradiation cells are kept for about 50 minutes outside of the CO2 incubator, care has to be taken to avoid alkalisation.
Hvis der anvendes svage buffere som f.eks. EBSS, kan alkalisering undgås ved at inkubere cellerne ved 7,5 % CO2.
If weak buffers like EBSS are used this can be achieved by incubating the cells at 7,5 % CO2.
Hvis cellerne inkuberes ved kun 5 % CO2, skal der vælges en stærkere buffer.
If the cells are incubated at 5 % CO2 only, a stronger buffer should be selected.
Testkemikalier med begrænset opløselighed i vand skal opløses i et passende opløsningsmiddel.
Test chemicals of limited solubility in water should be dissolved in an appropriate solvent.
Hvis der anvendes opløsningsmiddel, skal det forefindes i et konstant volumen i alle kulturer, dvs. i de negative (opløsningsmiddel)kontroller og i alle koncentrationer af testkemikaliet, og det skal være ikke-cytotoksisk ved den pågældende koncentration.
If a solvent is used it must be present at a constant volume in all cultures, i.e. in the negative (solvent) controls as well as in all concentrations of the test chemical, and be noncytotoxic at that concentration.
Der skal vælges en sådan koncentration af testkemikaliet, at man undgår udfældning og uklare opløsninger.
Test chemical concentrations should be selected so as to avoid precipitate or cloudy solutions.
Dimethylsulfoxid (DMSO) og ethanol (EtOH) er de anbefalede opløsningsmidler.
Dimethylsulphoxide (DMSO) and ethanol (ETOH) are the recommended solvents.