natgillin/translations-raw huggingface dataset:
However, the intraperitoneal route is not recommended as it could expose the liver directly to the test substance rather than via the circulatory system.
Vendar intraperitonealni način ni priporočljiv, ker jetra lahko izpostavi preizkušam snovi neposredno in ne prek krvožilnega sistema.
Preparation of liver cells
Priprava jetrnih celic
Liver cell are prepared from treated animals normally 12-16 hours after dosing.
Jetrne celice tretiranih živali se navadno pripravijo 12 do 16 ur po odmerjanju.
An additional earlier sampling time (normally two to four hours post-treatment) is generally necessary unless there is a clear positive response at 12-16 hours.
Navadno je potrebno dodatno, zgodnejše vzorčenje (ponavadi dve do štiri ure po tretiranju), razen če se po 12 do 16 urah pokaže jasen pozitivni odziv.
However, alternative sampling times may be used when justified on the basis of toxicokinetic data.
Lahko se vzorči tudi ob drugih časih, kadar je to utemeljeno s podatki o toksikokinetiki.
Short-term cultures of mammalian liver cells are usually established by perfusing the liver in situ with collagenase and allowing freshly dissociated liver cells to attach themselves to a suitable surface.
Navadno se pripravijo kratkotrajne kulture jetrnih celic sesalcev, tako da se jetra perfundirajo in situ s kolagenazo in se sveže odcepljenim jetrnim celicam omogoči, da se pritrdijo na ustrezno podlago.
Liver cells from negative control animals should have a viability (5) of at least 50 %.
Jetrne celice živali negativne kontrole naj imajo sposobnost preživetja (5) vsaj 50 %.
Determination of UDS
Določanje UDS
Freshly isolated mammalian liver cells are incubated usually with medium containing 3H-TdR for an appropriate length of time, e.g. 3-8 hours.
Sveže izolirane sesalske jetrne celice se primerno dolgo, na primer tri do osem ur, inkubirajo, navadno v gojišču, ki vsebuje 3H-TdR.
At the end of the incubation period, medium should be removed from the cells, which may then be incubated with medium containing excess unlabelled thymidine to diminish unincorporated radioactivity (‘cold chase’).
Po končani inkubaciji se gojišče odstrani s celic, ki se nato lahko inkubirajo v gojišču s presežkom neoznačenega timidina, da se zmanjša nevgrajena radioaktivnost (cold chase).
The cells are then rinsed, fixed and dried.
Celice se nato sperejo, fiksirajo in posušijo.
For more prolonged incubation times, cold chase may not be necessary.
Pri daljši inkubaciji „cold chase“ morda ne bo potreben.
Slides are dipped in autoradiographic emulsion, exposed in the dark (e.g. refrigerated for 7-14 days), developed, stained, and exposed silver grains are counted.
Mikroskopski preparati se pomočijo v avtoradiografsko emulzijo, se izpostavijo v temi (npr. hranijo se v hladilniku 7 do 14 dni), se razvijejo in pobarvajo, nato se preštejejo izpostavljena srebrna zrnca.
Two to three slides are prepared from each animal.
Za vsako žival se pripravijo dva do trije preparati.
The slide preparations should contain sufficient cells of normal morphology to permit a meaningful assessment of UDS.
Mikroskopski preparati naj vsebujejo dovolj celic z normalno morfologijo, da je omogočeno smiselno ocenjevanje UDS.
Preparations are examined microscopically for signs of overt cytotoxicity (e.g. pyknosis, reduced levels of radiolabelling).
Preparati se mikroskopsko pregledajo, da se poiščejo znaki očitne citotoksičnosti (npr. piknoza, zmanjšana raven radioaktivnih označevalcev).
Slides should be coded before grain counting.
Mikroskopski preparati naj se kodirajo pred štetjem zrnc.
Individual slide and animal data should be provided.
Navedejo se podatki za posamezne mikroskopske preparate in živali.
Net nuclear grain (NNG) counts should be calculated for each cell, for each animal and for each dose and time by subtracting CG counts from NG counts.
Izračuna naj se neto število jedrnih zrnc (NNG) za vsako celico, vsako žival ter vsak odmerek in čas, tako da se od števila NG odšteje število CG.
If ‘cells in repair’ are counted, the criteria for defining ‘cells in repair’ should be justified and based on historical or concurrent negative control data.
Če se preštevajo „celice v popravljanju“, naj bodo merila za določanje „celic v popravljanju“ utemeljena in zasnovana na podatkih pretekle ali sočasne negativne kontrole.
Numerical results may be evaluated by statistical methods.
Numerični rezultati se lahko ovrednotijo s statističnimi metodami.
If used, statistical tests should be selected and justified prior to conducting the study.
Če se uporabijo statistični testi, naj se izberejo in utemeljijo pred začetkom študije.
Examples of criteria for positive/negative responses include:
Primeri meril za pozitivne/negativne odzive vključujejo:
positive
pozitivne
NNG values above a pre-set threshold which is justified on the basis of laboratory historical data; or
vrednosti NNG, večje od poprej določenega praga, ki je utemeljen na podlagi preteklih podatkov laboratorija; ali
NNG values significantly greater than concurrent control;
vrednosti NNG, znatno večje kakor pri sočasni kontroli;
negative
negativne
NNG values within/below historical control threshold; or
vrednosti NNG, v območju preteklega kontrolnega praga ali pod njim; ali
NNG values not significantly greater than concurrent control.
vrednosti NNG, ne znatno večje kakor pri sočasni kontroli.
The biological relevance of data should be considered: i.e. parameters such as inter-animal variation, dose-response relationship and cytotoxicity should be taken into account.
Prouči naj se biološka pomembnost rezultatov: to pomeni, naj se upoštevajo parametri, kakor so razlike med živalmi, odvisnost med odmerkom in odzivom ter citotoksičnost.
A positive result from the UDS test with mammalian liver cells in vivo indicate that a test substance induces DNA damage in mammalian liver cells in vivo that can be repaired by unscheduled DNA synthesis in vitro.
Pozitivni rezultat preizkusa UDS z jetrnimi celicami sesalcev in vivo pomeni, da preizkušana snov povzroča poškodbe DNA v jetrnih celicah sesalcev in vivo, ki se lahko popravijo z nenačrtno sintezo DNA in vitro.
A negative result indicates that, under the test conditions, the test substance does not induce DNA damage that is detectable by this test.
Negativni rezultat pomeni, da preizkušana snov pri preizkusnih pogojih ne povzroča poškodb DNA, ki se lahko zaznajo s tem preizkusom.
The likelihood that the test substance reaches the general circulation or specifically the target tissue (e.g. systemic toxicity) should be discussed.
Obravnava naj se verjetnost, da preizkušana snov doseže krvni obtok ali posebej tarčno tkivo (npr. sistemska toksičnost).
positive and negative vehicle/solvent controls,
pozitivni in negativni (nosilec/topilo) kontrolni vzorci,
methods for verifying that test agent reached the general circulation or target tissue, if applicable,
metode za preverjanje, ali je preizkušana snov dosegla krvni obtok ali tarčno tkivo, če je to primerno,
method of liver cell preparation and culture,
metoda priprave in kultiviranja jetrnih celic,
number of slides prepared and numbers of cells scored,
število pripravljenih mikroskopskih preparatov in število celic, upoštevanih pri štetju,
evaluation criteria,
merila vrednotenja,
criteria for considering studies as positive, negative or equivocal,
merila za določitev, ali je študija pozitivna, negativna ali dvoumna,
individual slide, animal and group mean values for nuclear grains, cytoplasmic grains, and net nuclear grains,
srednja vrednost števila jedrnih zrnc, števila citoplazemskih zrnc in neto števila jedrnih zrnc za posamezne mikroskopske preparate, živali in skupine,
dose-response relationship, if available,
odvisnost med odmerkom in odzivom, če je na voljo,
statistical evaluation if any,
statistična ocena, če je na voljo,
historical negative (solvent/vehicle) and positive control data with range, means and standard deviations,
podatki o pretekli negativni (topilo/nosilec) in pozitivni kontroli, z območji, srednjimi vrednostmi in standardnimi odkloni,
number of ‘cells in repair’ if determined,
število „celic v popravljanju“, če je bilo določeno,
number of S-phase cells if determined,
število celic v fazi S, če je bilo določeno,
viability of the cells.
sposobnost preživetja celic.
Ashby, J., Lefevre, P.A., Burlinson, B. and Penman, M.G., (1985) An Assessment of the In Vivo Rat Hepatocyte DNA Repair Assay.
Ashby, J., Lefevre, P.A., Burlinson, B. and Penman, M.G. (1985). An Assessment of the In Vivo Rat Hepatocyte DNA Repair Assay.
Mutation Res., 156, p. 1-18.
Mutation Res., 156, str. 1–18.
Butterworth, B.E., Ashby, J., Bermudez, E., Casciano, D., Mirsalis, J., Probst, G. and Williams, G., (1987) A Protocol and Guide for the In Vivo Rat Hepatocyte DNA-Repair Assay.
Butterworth, B.E., Ashby, J., Bermudez, E., Casciano, D., Mirsalis, J., Probst, G. and Williams, G. (1987). A Protocol and Guide for the In Vivo Rat Hepatocyte DNA-Repair Assay. Mutation Res.
Cambridge University Press, Cambridge, New York, Port Chester, Melbourne, Sydney, p. 52-77.
Cambridge University Press, Cambridge, New York, Port Chester, Melbourne, Sydney, str. 52–77.
Madle, S., Dean, S.W., Andrae, U., Brambilla, G., Burlinson, B., Doolittle, D.J., Furihata, C., Hertner, T., McQueen, C.A. and Mori, H., (1993) Recommendations for the Performance of UDS Tests In Vitro and In Vivo.
Madle, S., Dean, S.W., Andrae, U., Brambilla, G., Burlinson, B., Doolittle, D.J., Furihata, C., Hertner, T., McQueen, C.A. and Mori, H. (1993). Recommendations for the Performance of UDS Tests In Vitro and In Vivo.
Mutation Res., 312, p. 263-285.
Mutation Res., 312, str. 263–285.
Mutation Res., 291, p. 21-27.
Mutation Res., 291, str. 21–27.
Mirsalis, J.C., Tyson, C.K. and Butterworth, B.E., (1982) Detection of Genotoxic Carcinogens in the In Vivo/In Vitro Hepatocyte DNA Repair Assay.
Mirsalis, J.C., Tyson, C.K. and Butterworth, B.E. (1982).
Mutagen, 4, p. 553-562.
Mutagen, 4, str. 553–562.
This testing method is equivalent to the OECD TG 430 (2004).
Ta preskusna metoda je enakovredna OECD TG 430 (2004).
Skin corrosion refers to the production of irreversible tissue damage in the skin following the application of a test material (as defined by the Globally Harmonised System for the Classification and Labelling of Chemical Substances and Mixtures (GHS)) (1).
Jedkost za kožo pomeni nastanek nepovratnih poškodb kožnega tkiva po nanosu preskušanega materiala [po definiciji iz Globally Harmonised System for the Classification and Labelling of Chemical Substances and Mixtures (GHS)] (1).
This method provides a procedure by which the assessment of corrosivity is not carried out in live animals.
Ta metoda določa postopek, s katerim se ocena jedkosti ne opravlja na živih živalih.
The assessment of skin corrosivity has typically involved the use of laboratory animals (2).
Ocena jedkosti za kožo se je običajno opravljala na laboratorijskih živalih (2).
Concern for the pain and suffering of animals involved with this procedure has been addressed in the revision of testing method B.4 that allows for the determination of skin corrosion by using alternative, in vitro, methods, avoiding pain and suffering.
Zadržki v zvezi z bolečinami in trpljenjem živali, ki je povezano s tem postopkom, je bilo upoštevano v reviziji preskusne metode B.4, ki omogoča določevanje jedkosti za kožo z alternativnimi metodami in vitro, pri čemer se preprečita bolečina in trpljenje.
A first step towards defining alternative tests that could be used for skin corrosivity testing for regulatory purposes was the conduct of prevalidation studies (3).
V tej preskusni metodi se ocena jedkosti ne opravlja na živih živalih ali živalskem tkivu.
Following this, a formal validation study of in vitro methods for assessing skin corrosion (4)(5) was conducted (6)(7)(8).
Za temi je bila opravljena uradna validacijska študija metod in vitro za oceno jedkosti za kožo (4) (5) (6) (7) (8).
The outcome of these studies and other published literature led to the recommendation that the following tests could be used for the assessment of in vivo skin corrosivity (9)(10)(11): the human skin model test (see tesing method B.40bis) and the transcutaneous electrical resistance test (this method).
Na podlagi izidov teh študij in druge objavljene literature je bilo izdelano priporočilo, da se lahko naslednja preskusa uporabita za oceno jedkosti za kožo in vivo (9) (10) (11): preskus z modelom človeške kože (glej preskusno metodo B.40bis) in preskus transkutane električne upornosti (ta metoda).
A validation study and other published studies have reported that the rat skin transcutaneous electrical resistance (TER) assay (12)(13) is able to reliably discriminate between known skin corrosives and non-corrosives (5)(9).
V validacijski študiji in drugih objavljenih študijah so ugotovili, da lahko preskus transkutane električne upornosti (TER) pri podganah (12) (13) zanesljivo razlikuje med znanimi snovmi, ki so jedke za kožo, in znanimi snovmi, ki niso jedke (5) (9).
The test described in this method allows the identification of corrosive chemical substances and mixtures.
Preskus, opisan v tej metodi, omogoča identifikacijo jedkih kemijskih snovi in mešanic.
It further enables the identification of non-corrosive substances and mixtures when supported by a weight of evidence determination using other existing information (e.g. pH, structure-activity-relationships, human and/or animal data) (1)(2)(11)(14).
Omogoča tudi identifikacijo nejedkih snovi in mešanic, če je podprta z dokazi in ob uporabi drugih obstoječih podatkov (npr. pH, razmerja struktura-aktivnost, podatki o ljudeh in/ali živalih) (1) (2) (11) (14).
It does not provide information on skin irritation, nor does it allow the sub-categorisation of corrosive substances as permitted in the Globally Harmonised Classification System (GHS) (1).
Ne daje pa podatkov o draženju kože niti ne omogoča nadaljnje kategorizacije jedkih snovi, kot je to dovoljeno v Globally Harmonised Classification System (GHS) (1).
For a full evaluation of local skin effects after a single dermal exposure, it is recommended to follow the sequential testing strategy as appended to testing method B.4 (2) and provided in the Globally Harmonised System (1).
Za popolno vrednotenje lokalnih učinkov na kožo po enkratni izpostavljenosti se priporoča upoštevanje načrtovanja zaporednega preskušanja, ki je priloženo Preskusni metodi B.4 (2) in na voljo v Globally Harmonised System (1).
This testing strategy includes the conduct of in vitro tests for skin corrosion (as described in this method) and skin irritation before considering testing in live animals.
To načrtovanje preskušanja vključuje opravljanje preskusov jedkosti za kožo in vitro (kakor je opisano v tej metodi) in preskusov draženja kože pred preskušanjem na živih živalih.
Skin corrosionin vivo: is the production of irreversible damage of the skin: namely, visible necrosis through the epidermis and into the dermis, following the application of a test subsance for up to four hours.
Jedkost za kožoin vivo: je nastanek nepovratnih poškodb kože: zlasti, vidne nekroze skozi pokožnico in v usnjico v štirih urah po nanosu preskusne snovi.
Corrosive reactions are typified by ulcers, bleeding, bloody scabs, and, by the end of the observation at 14 days, by discolouration due to blanching of the skin, complete areas of alopecia, and scars.
Reakcije na jedkost se razvrstijo na ulceracije, krvavitve, krvave kraste in po 14-dnevnem opazovanju, ko se zaradi luščenja kože izgubi obarvanost, na območja alopecije in brazgotine.
Transcutaneous Electrical Resistance (TER): is a measure of the electrical impendance of the skin, as a resistance value in kilo Ohms.
Transkutana električna upornost (TER): merilo električne impedance kože, ki je izražena kot upornost v kiloohmih.
A simple and robust method of assessing barrier function by recording the passage of ions through the skin using a Wheatstone bridge apparatus.
Preprosta in robustna metoda za ocenjevanje pregradne funkcije z beleženjem prehoda ionov preko kože z aparaturo z Wheatstonovim mostičem.
Reference chemicals
Referenčne kemikalije
1,2-Diaminopropane
1,2-Diaminopropan
Severely corrosive
Močno jedko
Acrylic Acid
Akrilna kislina
Severely Corrosive
Močno jedko
2-tert. Butylphenol
2-terc-Butilfenol
Corrosive
Jedko
Potassium hydroxide (10 %)
Kalijev hidroksid (10-odstoten)
Sulfuric acid (10 %)
Zveplova kislina (10-odstotna)
Octanoic acid (caprylic acid)
Oktanojska (kaprilska kislina)
4-Amino-1,2,4-triazole
4-Amino-1,2,4-triazol
Not corrosive
Ni jedko
Tetrachloroethylene
Tetrakloroetilen
Isostearic acid
Izostearinska kislina
4-(Methylthio)-benzaldehyde
4-(Metiltio)-benzaldehid
Most of the chemicals listed are taken from the list of chemicals selected for the ECVAM international validation study (4).
Večina navedenih kemikalij je vzetih s seznama kemikalij izbranih za mednarodno validacijsko študijo ECVAM (4).
Their selection is based on the following criteria:
Izbira v tej študiji je temeljila na naslednjih kriterijih:
equal number of corrosive and non-corrosive substances;
enako število jedkih in nejedkih snovi;
commercially available substances covering most of the relevant chemical classes;
komercialno dostopne snovi, ki pokrivajo večino pomembnih kemijskih skupin;
inclusion of severely corrosive as well as less corrosive substances in order to enable discrimination based on corrosive potency;
vključitev močno jedkih in manj jedkih snovi, da se omogoči razlikovanje na podlagi stopnje jedkosti;
choice of chemicals that can be handled in a laboratory without posing other serious hazards than corrosivity.
izbira kemikalij, s katerimi je mogoče v laboratoriju ravnati, ne da bi nastopile druge hude nevarnosti z izjemo jedkosti.
The test material is applied for up to 24 hours to the epidermal surfaces of skin discs in a two-compartment test system in which the skin discs function as the separation between the compartments.
Preskušani material se nanese za največ 24 ur na epidermalne površine kožnih ploščic v preskusnem sistemu z dvema komorama, v katerem kožne ploščice ločujejo komori.
The skin discs are taken from humanely killed rats aged 28-30 days.
Kožne ploščice se odvzamejo s humano usmrčenih podgan, starih 28–30 dni.
Corrosive materials are identified by their ability to produce a loss of normal stratum corneum integrity and barrier function, which is measured as a reduction in the TER below a threshold level (12).
Jedki materiali se identificirajo glede na zmožnost zmanjšati celovitost in pregradno funkcijo rožene plasti pokožnice, ki se meri kot znižanje TER pod raven praga (12).
For rat TER, a cut-off value of 5 kΏ has been selected based on extensive data for a wide range of chemicals where the vast majority of values were either clearly well above (often > 10 kΩ), or well below (often < 3 kΩ) this value (12).
Za TER pri podganah je bil na podlagi obsežnih podatkov za širok obseg kemikalij izbran prag 5 kΩ, kjer je bila velika večina vrednosti precej nad pragom (pogosto > 10 kΩ) ali precej pod njim (pogosto < 3 kΩ) (12).
Generally, materials which are non-corrosive in animals but are irritating or non-irritating do not reduce the TER below this cut-off value.
Na splošno materiali, ki niso jedki za živali, ampak so dražilni ali nedražilni, ne znižujejo TER pod ta prag.
Furthermore, use of other skin preparations or other equipment may alter the cut-off value, necessitating further validation.
Prav tako lahko uporaba drugih kožnih pripravkov ali druge opreme spremeni vrednost praga, kar zahteva dodatne validacije.
A dye-binding step is incorporated into the test procedure for confirmation testing of positive results in the TER including values around 5 kΩ.
V preskusni postopek je vključena stopnja vezave barvila za potrjevanje pozitivnih rezultatov preskusa TER, kadar so vrednosti okoli 5 kΩ.
The dye-binding step determines if the increase in ionic permeability is due to physical destruction of the stratum corneum.
V stopnji vezave barvila se ugotovi, ali je povečanje ionske prepustnosti posledica fizičnega uničenja rožene plasti pokožnice.
The TER method utilising rat skin has shown to be predictive of in vivo corrosivity in the rabbit assessed under Testing Method B.4 (2).
Metoda TER je na podganji koži pokazala, da lahko pri kuncih napove jedkost in vivo, določeno s preskusno metodo B.4 (2).
It should be noted that the in vivo rabbit test is highly conservative with respect to skin corrosivity and skin irritation when compared with the human skin patch test (15).
Treba je pripomniti, da je preskus in vivo na kuncih v primerjavi s preskusom na koščku človeške kože zelo konzervativen glede jedkosti za kožo in draženja kože (15).
Rats are the species of choice because the sensitivity of their skin to chemicals in this test has been previously demonstrated (10).
Podgane so bile izbrane, ker je bila občutljivost kože podgan za kemikalije v tem preskusu predhodno dokazana (10).
The age (when the skin is collected) and strain of the rat is particularly important to ensure that the hair follicles are in the dormant phase before adult hair growth begins.
Zagotoviti je treba, da so mešički dlak v dormantni fazi, preden se začne rast odraslih dlak, pri čemer sta zlasti pomembna starost (ob odvzemu kože) in linija podgane.
The dorsal and flank hair from young, approximately 22 day-old, male or female rats (Wistar-derived or a comparable strain), is carefully removed with small clippers.
Dlaka na hrbtu in bokih mladih približno 22 dni starih samcev ali samic (Wistar ali podobne linije podgan) se previdno odstrani z majhnimi škarjami.
Then, the animals are washed by careful wiping, whilst submerging the clipped area in antibiotic solution (containing, for example, streptomycin, penicillin, chloramphenicol, and amphotericin, at concentrations effective in inhibiting bacterial growth).
Nato se živali s pazljivim brisanjem umijejo, ostrižena površina pa se potopi v antibiotično raztopino (ki denimo vsebuje streptomicin, penicilin, kloramfenikol in amfotericin v koncentracijah, ki učinkovito preprečujejo rast bakterij).
Animals are washed with antibiotics again on the third or fourth day after the first wash and are used within three days of the second wash, when the stratum corneum has recovered from the hair removal.
Živali se z antibiotično raztopino ponovno umijejo tretji ali četrti dan po prvem umivanju, uporabijo pa se v 3 dneh po drugem umivanju, ko rožena plast okreva po odstranitvi dlak.
Preparation of the skin discs
Priprava kožnih ploščic
Animals are humanely killed when 28-30 days old; this age is critical.
Živali se humano usmrtijo, ko so stare 28-30 dni; ta starost je ključna.
The dorso-lateral skin of each animal is then removed and stripped of excess subcutaneous fat by carefully peeling it away from the skin.
Z vsake posamezne živali se nato odstrani hrbtno bočna koža in z nje previdno odlušči vsa odvečna podkožna maščoba.
Skin discs, with a diameter of approximately 20 mm each, are removed.
Nato se izrežejo kožne ploščice v premeru približno 20 mm.
The skin may be stored before disks are used where it is shown that positive and negative control data are equivalent to that obtained with fresh skin.
Koža se lahko shrani pred uporabo ploščic, kadar se dokaže, da so podatki pozitivnih in negativnih kontrol enaki kot pri sveži koži.
Each skin disc is placed over one of the ends of a PTFE (polytetrafluoroethylene) tube, ensuring that the epidermal surface is in contact with the tube.
Vsaka kožna ploščica se namesti čez konec cevi iz PTFE (politetrafluoroetilena), pri čemer se mora površina pokožnice dotikati cevi.
A rubber ‘O’ ring is press-fitted over the end of the tube to hold the skin in place and excess tissue is trimmed away.
Čez konec cevi se tesno namesti gumijast obroč, s katerim se koža pričvrsti, nato se obreže odvečno tkivo.
Tube and ‘O’ ring dimensions are shown in Figure 2.
Mere cevi in obroča so prikazane na sliki 2.
The rubber ‘O’ ring is then carefully sealed to the end of the PTFE tube with petroleum jelly.
Gumijasti obroč se nato z naravnim vazelinom pazljivo pri tesni na konec PTFE-cevi.
The tube is supported by a spring clip inside a receptor chamber containing MgSO4 solution (154 mM) (Figure 1).
Cev se z vzmetno sponko namesti v receptorsko komoro, ki vsebuje raztopino MgSO4 (154 mM) (slika 1).