natgillin/translations-raw huggingface dataset:
Since RhE models are based on cells of human origin, they may predict these chemicals as non-irritant (UN GHS/EU CLP No Category).
Ker modeli rekonstruirane človeške pokožnice temeljijo na celicah človeškega izvora, lahko te kemikalije napovedo kot snovi, ki ne dražijo (brez kategorije po GHS ZN/CLP EU).
Required predictive values for sensitivity, specificity and overall accuracy for any similar or modified method to be considered valid
Zahtevane vrednosti napovedljivosti za občutljivost, specifičnost in splošno natančnost katere koli podobne ali spremenjene metode, ki se šteje za veljavno
Overall Accuracy
Splošna natančnost
It is possible that one or several tests pertaining to one or more test chemicals does/do not meet the test acceptance criteria for the test and control chemicals or is/are not acceptable for other reasons.
Lahko se zgodi, da eden ali več preskusov v zvezi z eno preskusno kemikalijo ali več preskusnimi kemikalijami ne izpolnjuje meril za sprejemljivost preskusa za preskusne in kontrolne kemikalije ali pa ni sprejemljiv zaradi drugih razlogov.
To complement missing data, for each test chemical a maximum number of two additional tests is admissible (“retesting”).
Za dopolnitev manjkajočih podatkov je za vsako preskusno kemikalijo dopustna izvedba največ dveh dodatnih preskusov (‚ponovno preskušanje‘).
More precisely, since in case of retesting also PC and NC have to be concurrently tested, a maximum number of two additional runs may be conducted for each test chemical.
Natančneje, ker je treba v primeru ponovnega preskušanja primerjalno preskusiti tudi pozitivno in negativno kontrolo, sta lahko za vsako preskusno kemikalijo izvedeni največ dve dodatni ponovitvi.
It is conceivable that even after retesting, the minimum number of three valid runs required for each tested chemical is not obtained for every Reference Chemical in every participating laboratory, leading to an incomplete data matrix.
Obstaja verjetnost, da vsak sodelujoči laboratorij za vsako referenčno kemikalijo tudi po ponovnem preskušanju ne bo dobil vsaj treh veljavnih ponovitev, zahtevanih za vsako preskušano kemikalijo, zaradi česar bo podatkovna matrika nepopolna.
In such cases the following three criteria should all be met in order to consider the datasets acceptable:
Da se zbirka podatkov štela za popolno, je treba v takih primerih izpolniti naslednja tri merila:
All 20 Reference Chemicals should have at least one complete run sequence.
pri vseh 20 referenčnih kemikalijah mora biti vsaj eno zaporedje ponovitev izvedeno v celoti;
In each of at least three participating laboratories, a minimum of 85 % of the run sequences need to be complete (for 20 chemicals; i.e. 3 invalid run sequences are allowed in a single laboratory).
v vsakem od vsaj treh sodelujočih laboratorijev mora biti v celoti izvedenih vsaj 85 % zaporedij ponovitev (za 20 kemikalij; tj. v enem laboratoriju so dovoljena 3 neveljavna zaporedja ponovitev);
A minimum of 90 % of all possible run sequences from at least three laboratories need to be complete (for 20 chemicals tested in 3 laboratories; i.e. 6 invalid run sequences are allowed in total).
v celoti izvedenih mora biti vsaj 90 % vseh zaporedij ponovitev iz vsaj treh laboratorijev (za 20 kemikalij, preskušanih v treh laboratorijih, tj. skupno je dovoljenih 6 neveljavnih zaporedij ponovitev).
The chemical selection is based on the following criteria: (i) the chemicals are commercially available; (ii) they are representative of the full range of Draize irritancy scores (from non-irritant to strong irritant); (iii) they have a well-defined chemical structure; (iv) they are representative of the chemical functionality used in the validation process; and (v) they are not associated with an extremely toxic profile (e.g. carcinogenic or toxic to the reproductive system) and they are not associated with prohibitive disposal costs.
Izbor kemikalij temelji na naslednjih merilih: (i) kemikalije so na voljo na tržišču, (ii), predstavljajo celoten niz rezultatov preskusa Draize za draženje kože (od nerazdražene do zelo razdražene kože), (iii) njihova kemična struktura je natančno opredeljena, (iv) predstavljajo kemijsko delovanje, ki je uporabljeno v validacijskem postopku, in (v), niso povezane z zelo strupenim profilom (npr. rakotvornim ali strupenim za reprodukcijski sistem) ali stroški zaradi prepovedane izpostavljenosti tem kemikalijam.
Chemicals that are irritant in the rabbit but for which there is reliable evidence that they are non-irritant in humans (31) (32) (33).
Kemikalije, ki so dražilne za kunce, vendar obstajajo zanesljivi dokazi, da niso dražilne za ljudi (31) (32) (33).
Under the UN GHS, not in the EU CLP
Po GHS ZN, ne po CLP EU.
The following Chapters are added:
Dodajo se naslednja poglavja:
IN VITRO MAMMALIAN CELL MICRONUCLEUS TEST
PRESKUS MIKRONUKLEUSOV IN VITRO PRI CELICAH SESALCEV
The in vitro micronucleus (MNvit) assay is a genotoxicity test for the detection of micronuclei (MN) in the cytoplasm of interphase cells.
Analiza mikronukleusov in vitro je preskus genotoksičnosti za odkrivanje mikronukleusov v citoplazmi interfaznih celic.
Micronuclei may originate from acentric chromosome fragments (i.e. lacking a centromere), or whole chromosomes that are unable to migrate to the poles during the anaphase stage of cell division.
Mikronukleusi lahko izvirajo iz acentričnih kromosomskih delcev (tj. brez centromere) ali celih kromosomov, ki med anafazo celične delitve ne morejo potovati na pole.
The assay detects the activity of clastogenic and aneugenic chemicals (substances and mixtures) (1) (2) in cells that have undergone cell division during or after exposure to the test substance.
Analiza odkriva delovanje kemikalij, ki povzročajo strukturne in številčne poškodbe kromosomov (klastogene in anevgene snovi in zmesi) (1) (2) v celicah, pri katerih je med izpostavljenostjo preskusni snovi ali po njej prišlo do delitve celic.
This Test Method (TM) allows the use of protocols with and without the actin polymerisation inhibitor cytochalasin B (cytoB).
Ta preskusna metoda omogoča uporabo protokolov z inhibitorjem polimerizacije aktina citohalazina B (citoB).
The addition of cytoB prior to the targeted mitosis allows for the identification and selective analysis of micronucleus frequency in cells that have completed one mitosis because such cells are binucleate (3) (4).
Dodatek citohalazina B pred načrtovano mitozo omogoča določitev in selektivno analizo frekvence mikronukleusov v celicah, v katerih se je zaključila ena mitoza, ker imajo takšne celice dve jedri (3) (4).
This TM also allows the use of protocols without cytokinesis block, provided there is evidence that the cell population analysed has undergone mitosis.
Ta preskusna metoda omogoča uporabo protokolov brez citokinetskega bloka, če obstajajo dokazi, da je pri analizirani celični populaciji prišlo do mitoze.
Micronuclei represent damage that has been transmitted to daughter cells, whereas chromosome aberrations scored in metaphase cells may not be transmitted.
Mikronukleusi predstavljajo poškodbo, ki je bila prenesena na hčerinske celice, pri čemer se kromosomske aberacije v metafaznih celicah ne morejo prenesti.
Because micronuclei in interphase cells can be assessed relatively objectively, laboratory personnel need only determine whether or not the cells have undergone division and how many cells contain a micronucleus.
Ker se lahko mikronukleusi v interfaznih celicah ocenijo razmeroma objektivno, mora laboratorijsko osebje ugotoviti samo, ali so se celice delile in koliko celic vsebuje mikronukleus.
As a result, the preparations can be scored relatively quickly and analysis can be automated.
Zato se lahko pripravke določi razmeroma hitro, analiza pa je lahko avtomatizirana.
This makes it practical to score thousands instead of hundreds of cells per treatment, increasing the power of the assay.
Zaradi tega se lahko pri vsakem tretiranju oceni na tisoče namesto na stotine celic, s čimer se poveča moč analize.
Finally, as micronuclei may arise from lagging chromosomes, there is the potential to detect aneuploidy-inducing agents that are difficult to study in conventional chromosomal aberration tests, e.g. OECD Test Guideline 473 (Chapter B.10 of this Annex) (17).
Ker lahko mikronukleusi nastanejo zaradi zaostalih kromosomov, obstaja možnost odkritja snovi, ki povzročajo anevploidijo in se pri klasičnih preskusih kromosomskih aberacij, glej npr. Smernico za preskušanje OECD 473 (poglavje B.10 te priloge), težko preučujejo (17).
However, the MNvit assay does not allow for the differentiation of chemicals inducing polyploidy from those inducing clastogenicity without special techniques such as FISH described under paragraph 2.
Vendar analiza mikronukleusov in vitro ne omogoča razlikovanja kemikalij, ki povzročajo poliploidijo, od tistih, ki povzročajo klastogenost, brez posebnih tehnik, kot je fluorescenčna in situ hibridizacija (FISH), opisana v odstavku 2.
The MNvit assay is an in vitro method that typically uses cultured human or rodent cells.
Analiza mikronukleusov in vitro je metoda, pri kateri se običajno uporabljajo gojene človeške celice ali celice glodavcev.
It provides a comprehensive basis for investigating chromosome damaging potential in vitro because both aneugens and clastogens can be detected.
Zagotavlja celovito podlago za preiskovanje morebitnih poškodb kromosomov in vitro, saj lahko odkriva snovi, ki povzročajo strukturne in številčne poškodbe kromosomov (anevgene in klastogene).
These include, in particular, the international validation studies coordinated by the Société Française de Toxicologie Génétique (SFTG) (18) (19) (20) (21) (22) and the reports of the International Workshop on Genotoxicity Testing (4) (16).
Ti vključujejo zlasti mednarodne validacijske študije, ki jih usklajuje Société Française de Toxicologie Génétique (SFTG) (18) (19) (20) (21) (22), in poročila International Workshop on Genotoxicity Testing (4) (16).
The available data have also been re-evaluated in a weight-of-evidence retrospective validation study by the European Centre for the Validation of Alternative Methods (ECVAM) of the European Commission, and the test method has been endorsed as scientifically valid by the ECVAM Scientific Advisory Committee (ESAC) (32) (33) (34).
Razpoložljivi podatki so bili tudi ponovno ocenjeni v retrospektivni validacijski študiji glede zanesljivosti dokazov, ki jo je izvedel Evropski center za validacijo alternativnih metod (ECVAM) Evropske komisije, Znanstveni svetovalni odbor ECVAM (ESAC) pa je preskusno metodo potrdil kot znanstveno veljavno (32) (33) (34).
The use of the human TK6 lymphoblastoid cell line (35), HepG2 cells (36) (37) and primary Syrian Hamster Embryo cells (38) has been described, although they have not been used in validation studies.
Opisana je bila uporaba celičnih linij človeških limfoblastov TK6 (35), celic HepG2 (36) (37) in primarnih embrionalnih celic sirijskega hrčka (38), čeprav v validacijskih študijah niso bile uporabljene.
Tests conducted in vitro generally require the use of an exogenous source of metabolic activation unless the cells are metabolically competent with respect to the substances being tested.
Pri preskusih, izvedenih in vitro, je treba običajno uporabiti zunanji vir aktivacije presnove, razen če so celice glede na snovi, ki se preskušajo, sposobne presnavljanja.
The exogenous metabolic activation system does not entirely mimic in vivo conditions.
Zunanji sistem aktivacije presnove ne posnema pogojev in vivo v celoti.
Care should also be taken to avoid conditions that would lead to artefactual positive results which do not reflect intrinsic mutagenicity, and may arise from such factors as marked changes in pH or osmolality, or by high levels of cytotoxicity (39) (40) (41).
Treba je tudi paziti, da se prepreči nastanek razmer, ki bi vodile do nepravilnih pozitivnih rezultatov, ki ne kažejo prave mutagenosti in so lahko posledica dejavnikov, kot je opazna sprememba pH ali osmolarnosti ali visoka raven citotoksičnosti (39) (40) (41).
If the test chemical causes a change in the pH of the medium at the time of addition, the pH should be adjusted, preferably by buffering the stock solution so that all the volumes at all test concentrations, and for all controls, remain the same.
Če preskusna kemikalija v času dodajanja v medij vpliva na spremembo pH, je treba pH prilagoditi, po možnosti z dodajanjem pufra v založno raztopino, tako da vsi volumni pri vseh preskusnih koncentracijah in za vse kontrole ostanejo enaki.
To analyse the induction of micronuclei, it is essential that mitosis has occurred in both treated and untreated cultures.
Za analizo nastanka mikronukleusov je bistvenega pomena, da je do mitoze prišlo v tretiranih in netretiranih kulturah.
The most informative stage for scoring micronuclei is in cells that have completed one mitosis during or after treatment with the test substance.
Glede štetja mikronukleusov se največ podatkov pridobi s pomočjo celic, v katerih se je med tretiranjem s preskusno snovjo ali po njej zaključila ena mitoza.
Cell cultures of human or mammalian origin are exposed to the test substance both with and without an exogenous source of metabolic activation unless cells with an adequate metabolising capability are used.
Človeške celične kulture ali celične kulture sesalcev so izpostavljene preskusni snovi z zunanjim virom aktivacije presnove ali brez nje, razen če so uporabljene celice z ustrezno sposobnostjo presnavljanja.
Concurrent solvent/vehicle (VC) and positive control chemicals (PC) are included in all tests.
V vsak preskus so vključene primerjalne (topilo/nosilec) kemikalije in kemikalije pozitivne kontrole.
During or after exposure to the test substance, the cells are grown for a period sufficient to allow chromosome or spindle damage to lead to the formation of micronuclei in interphase cells.
Med izpostavljenostjo preskusni snovi ali po njej se celice gojijo tako dolgo, dokler zaradi poškodbe kromosoma ali vretena v interfaznih celicah ne pride do nastanka mikronukleusov.
For induction of aneuploidy, the test substance should ordinarily be present during mitosis.
Za nastanek anevploidije mora biti med mitozo navadno prisotna preskusna snov.
Harvested and stained interphase cells are analysed for the presence of micronuclei.
Odvzete in obarvane interfazne celice se analizirajo glede prisotnosti mikronukleusov.
Ideally, micronuclei should only be scored in those cells that have completed mitosis during exposure to the test substance or during the post-exposure period, if one is used.
Po možnosti se mikronukleuse šteje samo v tistih celicah, v katerih je med izpostavljenostjo preskusni snovi ali v obdobju po izpostavljenosti, če se uporabi, prišlo do mitoze.
In cultures that have been treated with a cytokinesis blocker, this is achieved by scoring only binucleate cells.
V kulturah, ki so bile tretirane s citokinetskim blokom, se to doseže s štetjem samo celic z dvema jedroma.
In the absence of a cytokinesis blocker, it is important to demonstrate that the cells analysed are likely to have undergone cell division during or after exposure to the test substance.
Če citokinetski blok ni bil uporabljen, je treba dokazati, da bi pri analiziranih celicah verjetno prišlo do deljenja celic med izpostavljenostjo preskusni snovi ali po njej.
For all protocols, it is important to demonstrate that cell proliferation has occurred in both the control and treated cultures, and the extent of test substance-induced cytotoxicity or cytostasis should be assessed in the cultures (or in parallel cultures) that are scored for micronuclei.
Pri vseh protokolih je treba dokazati, da je do množenja celic prišlo v kontrolnih in tretiranih kulturah, v kulturah (ali vzporednih kulturah), pri katerih se štejejo mikronukleusi, pa je treba oceniti obseg citotoksičnosti ali citostaze, ki je nastala zaradi preskusne snovi.
Cultured primary human peripheral blood lymphocytes (5) (19) (42) (43) and a number of rodent cell lines such as CHO, V79, CHL/IU, and L5178Y cells may be used (18) (19) (20) (21) (22) (25) (26) (27) (28) (30).
Lahko se uporabijo gojeni primarni človeški limfociti periferne krvi (5) (19) (42) (43) in številne celične linije glodavcev, kot so celice CHO, V79, CHL/IU, in L5178Y (18) (19) (20) (21) (22) (25) (26) (27) (28) (30).
The use of other cell lines and types should be justified based on their demonstrated performance in the assay, as described in the Acceptability Criteria section.
Uporabo drugih celičnih linij in vrst je treba utemeljiti na podlagi njihove dokazane učinkovitosti v analizi, kot je opisano v oddelku Merila za sprejemljivost.
Because the background frequency of micronuclei will influence the sensitivity of the assay, it is recommended that cell types with a low, stable background frequency of micronucleus formation be used.
Ker pogostost mikronukleusov v ozadju vpliva na občutljivost analize, se priporoča uporaba celičnih vrst z nizko, stabilno pogostostjo nastajanja mikronukleusov v ozadju.
Human peripheral blood lymphocytes should be obtained from young (approximately 18-35 years of age), healthy, non-smoking individuals with no known recent exposures to genotoxic chemicals or radiation.
Človeški limfociti periferne krvi se pridobijo od mladih (starih približno 18–35 let), zdravih posameznikov, ki ne kadijo in ki v zadnjem času niso bili izpostavljeni genotoksičnim kemikalijam ali sevanju.
If cells from more than one donor are pooled for use, the number of donors should be specified.
Če so za uporabo zbrane celice od več kot enega donatorja, je treba določiti število donatorjev.
The micronucleus frequency increases with age and this trend is more marked in females than in males (44) and this should be taken into account in the selection of donor cells for pooling.
Pogostost mikronukleusov se povečuje z leti, ta trend pa je bolj opazen pri ženskah kot pri moških (44), kar je treba pri upoštevati pri izbiri donorskih celic.
Appropriate culture medium and incubation conditions (culture vessels, CO2 concentration, temperature, and humidity) should be used for maintaining cultures.
Pri vzdrževanju kultur se uporabijo ustrezna gojišča za kulture in pogoji inkubacije (posode za kulture, koncentracija CO2, temperatura in vlažnost).
Established cell lines and strains should be checked routinely for the stability of the modal chromosome number and the absence of mycoplasma contamination, and should not be used if contaminated or if the modal chromosome number has changed.
Trajne celične linije in sevi se redno preverjajo, ali je v njih modalno kromosomsko število stabilno in ali niso okužene z mikoplazmo; okužene celične linije in sevi naj se ne uporabljajo.
The normal cell cycle time for the culture conditions used in the testing laboratory should be known.
Poznati je treba običajni čas celičnega ciklusa za pogoje gojenja, ki se uporabljajo v preskuševalnem laboratoriju.
If the cytokinesis-block method is used then the concentration of the cytokinesis inhibitor should be optimised for the particular cell type and should be shown to produce a good yield of binucleate cells for scoring.
Če se uporablja metoda citokinetskega bloka, mora biti koncentracija citokinetskega inhibitorja prilagojena določeni vrsti celic in dokazano mora biti, da zagotavlja dober izkoristek celic z dvema jedroma za štetje.
Established cell lines and strains: cells are propagated from stock cultures, seeded in culture medium at a density such that the cultures will not reach confluency in monolayers, and suspension cultures will not reach excessive density before the time of harvest, and incubated at 37 °C.
Trajne celične linije in sevi: celice se namnožijo iz založnih kultur, nasadijo v gojišče tako na gosto, da kultura ne bo dosegla konfluentne rasti v enojnih plasteh in kulture suspenzije ne bodo dosegle prevelike gostote preden se požanjejo, in se inkubirajo pri 37 °C.
Lymphocytes: whole blood treated with an anti-coagulant (e.g. heparin), or separated lymphocytes, are cultured in the presence of a mitogen e.g. phytohaemagglutinin (PHA) prior to exposure to the test substance and cytoB.
Limfociti: celotna kri, tretirana z antikoagulantom (npr. heparinom), ali ločeni limfociti, so gojeni ob prisotnosti mitogena, npr. fitohemaglutinina (PHA) pred izpostavljenostjo preskusni snovi in citohalazinu B.
Metabolic activation
Aktivacija presnove
Exogenous metabolising systems should be used when using cells with inadequate endogenous metabolic capacity.
Pri uporabi celic z neustrezno notranjo sposobnostjo presnavljanja je treba uporabiti zunanje presnovne sisteme.
The most commonly used system is a co-factor-supplemented post-mitochondrial fraction (S9) prepared from the livers of rodents treated with enzyme-inducing agents such as Aroclor 1254 (45) (46) or a combination of phenobarbitone and β-naphthoflavone (46) (47) (48) (49).
Najpogosteje uporabljani sistem je postmitohondrijska frakcija z dodanim kofaktorjem (S9), pripravljena iz jeter glodavcev, ki so bila tretirana s sredstvi za encimsko indukcijo, kot je Aroclor 1254 (45) (46), ali z zmesjo fenobarbitona in β-naftoflavona (46) (47) (48) (49).
The latter combination does not conflict with the Stockholm Convention on Persistent Organic Pollutants (50) and Regulation (EC) No 850/2004 on Persistent Organic Pollutants (66) and has been shown to be as effective as Aroclor 1254 for inducing mixed-function oxidases (46) (47) (48) (49).
Slednja kombinacija ni v nasprotju s Stockholmsko konvencijo o obstojnih organskih onesnaževalih (50) in Uredbo (ES) št. 850/2004 o obstojnih organskih onesnaževalih (66), za nastanek oksidaz z mešano funkcijo pa se je v primerjavi s sredstvom Aroclor 1254 izkazala kot enako učinkovita (46) (47) (48) (49).
The S9 fraction typically is used at concentrations ranging from 1-10 % (v/v) in the final test medium.
Postmitohondrijska frakcija se običajno uporablja v koncentracijah 1–10 % (v/v) v končnem preskusnem gojišču.
The condition of a metabolic activation system may depend upon the class of chemical being tested and in some cases it may be appropriate to utilise more than one S9 concentration.
Pogoji sistema za aktivacijo presnove so lahko odvisni od skupine preskušane kemikalije in včasih je primerno uporabiti več kot eno koncentracijo S9.
Genetically engineered cell lines expressing specific human or rodent activating enzymes may eliminate the need for an exogenous metabolic activation system, and may be used as the test cells.
Gensko spremenjene celične linije, v katerih se izražajo geni za točno določene aktivirajoče človeške encime ali encime glodavcev, lahko odpravijo potrebo po zunanjem sistemu aktivacije presnove in se lahko uporabijo kot preskusne celice.
In such cases the choice of the cell lines used should be scientifically justified, e.g. by relevance of the mixed function oxidases for the metabolism of the test substance (51), and their responsiveness to known clastogens and aneugens (see separate section on Acceptability Criteria).
V takih primerih mora biti izbira uporabljenih celičnih linij znanstveno utemeljena, npr. s pomembnostjo oksidaze z mešano funkcijo za presnovo preskusne snovi (51) in njihovo odzivnostjo na znane snovi, ki povzročajo strukturne in številčne poškodbe kromosomov (anevgene in klastogene) (glej oddelek Merila za sprejemljivost).
It should be recognised that the substance being tested may not be metabolised by the expressed mixed function oxidase(s); in this case, the negative results would not indicate that the test substance cannot induce micronuclei.
Priznati je treba, da izražene oksidaze z mešano funkcijo morda ne bodo presnavljale snovi, ki se preskuša; v takem primeru negativni rezultati ne bi pomenili, da preskusna snov ne more spodbuditi nastanka mikronukleusov.
Test substance preparation
Priprava preskusne snovi
Solid chemicals should be dissolved in appropriate solvents or vehicles and diluted, if appropriate, prior to treatment of the cells.
Trdne kemikalije se pred obdelavo celic raztopijo v ustreznih topilih ali nosilcih, in po potrebi razredčijo.
Liquid chemicals may be added directly to the test systems and/or diluted prior to treatment.
Tekoče kemikalije se lahko dodajo neposredno v preskusni sistem in/ali se pred obdelavo razredčijo.