natgillin/translations-raw huggingface dataset:
The test report must include the requirements stipulated in the protocol, including a justification for the test system used and should comprise the following:
Poročilo o preskusu mora vsebovati zahteve, določene v protokolu, vključno z utemeljitvijo uporabljenega sistema preskusa, ter tudi naslednje:
identification data (e.g. CAS number, if available, source, purity (radiochemical purity), known impurities, lot number),
identifikacijski podatki [npr. številka CAS, če je na voljo; vir; čistost (radiokemijska čistost); znane nečistoče; serijska številka]
physical nature, physicochemical properties (e.g. pH, volatility, solubility, stability, molecular weight and log Pow).
agregatno stanje, fizikalno-kemijske lastnosti (npr. pH, hlapnost, topnost, stabilnost, molekulska masa in log Pow).
Test preparation:
Preskusni pripravek:
formulation and justification of use,
pripravek in utemeljenost uporabe,
details of the test preparation, amount applied, achieved concentration, vehicle, stability and homogeneity.
podrobnosti preskusnega pripravka, količina nanosa, dosežena koncentracija, nosilec, stabilnost in homogenost.
Test animal:
Preskusna žival:
source of animals, housing conditions, diets, etc.,
vir živali, namestitveni pogoji, prehrana, itd.,
individual animal weights at start of test.
teže posameznih živali ob začetku preskusa.
details of the administration of the test preparation (site of application, assay methods, occlusion/non-occlusion, volume, extraction, detection),
podrobnosti uporabe preskusnega pripravka (mesto nanosa, preskusne metode, zaprtost/nezaprtost, prostornina, ekstrakcija, zaznavnost),
any signs of toxicity,
kakršni koli znaki toksičnosti,
tabulated absorption data (expressed as rate, amount or percentage),
tabelirani absorpcijski podatki (izraženi kot hitrost, količina in odstotek),
overall recoveries of the experiment,
celotni izkoristek poskusa,
interpretation of the results, comparison with any available data on percutaneous absorption of the test compound.
razlaga rezultatov, primerjava z razpoložljivimi podatki o absorpciji skozi kožo preskusne spojine.
ECETOC, (1993) Percutaneous Absorption.
ECETOC (1993) Perkutana absorpcija.
An example of a design of a typical device used to define and protect dermal application site during in vivo percutaneous absorption studies
Primer oblike značilne naprave, ki se uporablja za določanje in zaščito dermalnega mesta nanosa med in vivo študijami perkutane absorpcije
Activated charcoal filter or gauze cover
Aktivni ogleni filter ali gaza
Screw-threaded cap
Pokrov na vijačni navoj
Screw-threaded base
Osnova na vijačni navoj
Cyanoacrylate glue
Cianoakrilatno lepilo
This testing method is equivalent to the OECD TG 428 (2004).
Ta preskusna metoda je enakovredna OECD TG 428 (2004).
This method has been designed to provide information on absorption of a test substance applied to excised skin.
Ta metoda je bila oblikovana za zagotavljanje informacij o absorpciji preskusne snovi, nanesene na izrezano kožo.
It can either be combined with the method for skin absorption: in vivo method (1), or be conducted separately.
Lahko se kombinira z metodo za absorpcijo skozi kožo: metodo in vivo (1), ali pa se opravi ločeno.
It is recommended that the OECD Guidance Document for the Conduct of Skin Absorption Studies (2) be consulted to assist in the design of studies based on this method.
Priporočljivo je, da se preverijo Napotki OECD za izvajanje študij o absorpciji skozi kožo (2), kot pomoč pri oblikovanju študij, ki temeljijo na tej metodi.
The Guidance Document has been prepared to facilitate the selection of appropriate in vitro procedures for use in specific circumstances, to ensure the reliability of results obtained by this method.
Napotki so bili pripravljeni, da bi omogočili izbiro ustreznih in vitro postopkov za uporabo v posebnih okoliščinah, zaradi zagotavljanja zanesljivosti rezultatov, pridobljenih s to metodo.
The methods for measuring skin absorption and dermal delivery can be divided into two categories: in vivo and in vitro.
Metode za merjenje absorpcije skozi kožo in dermalne dostave so razdeljene v dve kategoriji: in vivo ter in vitro.
In vivo methods on skin absorption are well established and provide pharmacokinetic information in a range of animal species.
Metode absorpcije skozi kožo in vivo so zelo uveljavljene in zagotavljajo farmakokinetične informacije pri številnih živalskih vrstah.
An in vivo method is separately described in another testing method (1).
Metoda in vivo je opisana posebej v drugi preskusni metodi (1).
In vitro methods have also been used for many years to measure skin absorption.
Metode in vitro se tudi že dolgo uporabljajo za merjenje absorpcije skozi kožo.
Although formal validation studies of the in vitro methods covered by this testing method have not been performed, OECD experts agreed in 1999 that there was sufficient data evaluated to support the in vitro method (3).
Čeprav formalne validacijske študije metod in vitro, ki so zajete v to preskusno metodo, niso bile opravljene, so se strokovnjaki OECD leta 1999 dogovorili, da je v podporo metodi in vitro (3) ovrednotenih dovolj podatkov.
Further details that substantiate this support, including a significant number of direct comparisons of in vitro and in vivo methods, are provided with the Guidance Document (2).
Dodatni podrobni podatki, ki krepijo to podporo, vključno s pomembnim številom neposrednih primerjav med metodama in vitro ter in vivo, so zagotovljeni v Napotkih (2).
There are a number of monographs that review this topic and provide detailed background on the use of an in vitro method (4)(5)(6)(7)(8)(9)(10)(11)(12).
Ta tema je obravnavana v številnih monografijah, ki tudi navajajo podrobno ozadje uporabe metode in vitro (4) (5) (6) (7) (8) (9) (10) (11) (12).
In vitro methods measure the diffusion of chemicals into and across skin to a fluid reservoir and can utilise non-viable skin to measure diffusion only, or fresh, metabolically active skin to simultaneously measure diffusion and skin metabolism.
Z metodami in vitro se meri difuzija kemikalij v kožo in po koži v posodo s tekočino, uporablja pa se lahko neaktivna koža za merjenje samo difuzije, ali sveža, presnovno aktivna koža za istočasno merjenje difuzije in kožne presnove.
Such methods have found particular use as a screen for comparing delivery of chemicals into and through skin from different formulations and can also provide useful models for the assessment of percutaneous absorption in humans.
Take metode so postale posebno uporabne kot sito za primerjanje dostave kemikalij iz različnih pripravkov v in skozi kožo, lahko pa so tudi uporabni modeli za ocenjevanje absorpcije skozi kožo pri človeku.
The in vitro method may not be applicable for all situations and classes of chemicals.
Metode in vitro ni mogoče uporabljati za vsa stanja in razrede kemikalij.
It may be possible to use the in vitro test method for an initial qualitative evaluation of skin penetration.
Preskusno metodo in vitro je mogoče uporabljati za začetno kakovostno presojo penetracije skozi kožo.
In certain cases, it may be necessary to follow this up with in vivo data.
V določenih primerih je treba to metodo dopolniti s podatki iz metode in vivo.
The guidance document (2) should be consulted for further elaboration of situations where the in vitro method would be suitable.
Za nadaljnjo razčlenitev stanj, v katerih bi bila metoda in vitro ustrezna, je treba preveriti napotke (2).
Additional detailed information to support the decision is provided in (3).
Dodatne podrobne informacije v podporo odločitvi so na voljo v (3).
This method presents general principles for measuring dermal absorption and delivery of a test substance using excised skin.
Ta metoda predstavlja splošna načela merjenja dermalne absorpcije in dostave preskusne snovi pri uporabi izrezane kože.
Skin from many mammalian species, including humans, can be used.
Uporablja se lahko koža več vrst sesalcev, vključno s človekom.
The permeability properties of skin are maintained after excision from the body because the principal diffusion barrier is the non-viable stratum corneum; active transport of chemicals through the skin has not been identified.
Značilnosti prepustnosti kože se po odstranitvi s teles ohranjajo, ker je glavna difuzij ska pregrada neaktivna stratum corneum; aktivni prenos kemikalij skozi kožo ni identificiran.
The skin has been shown to have the capability to metabolise some chemicals during percutaneous absorption (6), but this process is not rate limiting in terms of actual absorbed dose, although it may affect the nature of the material entering the bloodstream.
Pokazalo se je, da ima koža zmožnost presnavljanja nekaterih kemikalij med perkutano absorpcijo (6), vendar ta postopek ne omejuje hitrosti dejansko absorbiranega odmerka, čeprav lahko vpliva na naravo snovi, ki vstopa v krvni obtok.
Absorbed dose (in vitro): mass of test substance reaching the receptor fluid or systemic circulation within a specified period of time.
Absorbirani odmerek(in vitro): masa preskusne snovi, ki pride do receptorske tekočine ali obtoka v sistemu v določenem časovnem obdobju.
Absorbable dose (in vitro): represents that present on or in the skin following washing.
Absorpcijski odmerek(in vitro): pomeni odmerek, prisoten na ali v koži po izpiranju.
The test substance, which may be radiolabelled, is applied to the surface of a skin sample separating the two chambers of a diffusion cell.
Preskusno snov, ki je lahko označena z radioaktivnim izotopom, se nanese na površino vzorca kože, ki ločuje dve komori difuzijske celice.
The chemical remains on the skin for a specified time under specified conditions, before removal by an appropriate cleansing procedure.
Kemikalija določen čas in pod določenimi pogoji ostane na koži, preden se odstrani po ustreznem postopku čiščenja.
The receptor fluid is sampled at time points throughout the experiment and analysed for the test chemical and/or metabolites.
Receptorska tekočina se v časovnih točkah vzorči med celotnim poskusom in analizirajo se preskusne kemikalije in/ali metaboliti.
When metabolically active systems are used, metabolites of the test chemical may be analysed by appropriate methods.
Če se uporabljajo presnovno aktivni sistemi, se z ustreznimi metodami lahko analizirajo metaboliti preskusnih kemikalij.
At the end of the experiment the distribution of the test chemical and its metabolites are quantified, when appropriate.
Na koncu poskusa se v celoti oceni razdelitev preskusnih kemikalij in njihovih metabolitov, kadar je ustrezno.
Using appropriate conditions, which are described in this method and the guidance document (2), absorption of a test substance during a given time period is measured by analysis of the receptor fluid and the treated skin.
Absorpcija preskusne snovi se meri v določenem časovnem obdobju pri ustreznih pogojih, ki so opisani v tej metodi in v napotkih (2), z analizo receptorske tekočine in obdelane kože.
The test substance remaining in the skin should be considered as absorbed unless it can be demonstrated that absorption can be determined from receptor fluid values alone.
Za preskusno snov, ki ostane v koži, se šteje, da je absorbirana, razen če je mogoče pokazati, da se absorpcija lahko določi le iz vrednosti receptorske tekočine.
Analysis of the other components (material washed off the skin and remaining within the skin layers) allows for further data evaluation, including total test substance disposition and percentage recovery.
Analiza drugih elementov (snovi, izprane s kože, ki ostane v plasteh kože) omogoča dodatno ovrednotenje podatkov, vključno s celotno razpoložljivostjo preskusne snovi in odstotkom izkoristka.
To demonstrate the performance and reliability of the test system in the performing laboratory, the results for relevant reference chemicals should be available and in agreement with published literature for the method used.
Za prikaz uspešnosti in zanesljivosti preskusnega sistema v izvajalnem laboratoriju, bi morali biti rezultati za ustrezne referenčne kemikalije na voljo in v skladu z objavljeno literaturo za uporabljeno metodo.
This requirement could be met by testing an appropriate reference substance (preferably of a lipophilicity close to the test substance) concurrently with the test substance or by providing adequate historical data for a number of reference substances of different lipophilicity (e.g. caffeine, benzoic acid, and testosterone).
To zahtevo je mogoče izpolniti s testiranjem ustrezne referenčne snovi (po možnosti z lipofilnostjo, ki je blizu preskusni snovi) hkrati s preskusno snovjo ali z zagotavljanjem dovolj preteklih podatkov za številne referenčne snovi z različno lipofilnostjo (npr. kofein, benzojska kislina in testosteron).
Diffusion cell
Difuzijska celica
A diffusion cell consists of a donor chamber and a receptor chamber between which the skin is positioned (an example of a typical design is provided in Figure 1).
Difuzijska celica je sestavljena iz donorske in receptorske komore, med katere se namesti koža (tipični primer je prikazan na Sliki 1).
The cell should provide a good seal around the skin, enable easy sampling and good mixing of the receptor solution in contact with the underside of the skin, and good temperature control of the cell and its contents.
Celica mora zagotoviti dobro zaščito okoli kože, omogočiti enostavno vzorčenje in dobro mešanje receptorske raztopine v stiku s spodnjo stranjo kože ter dober temperaturni nadzor celice in njene vsebine.
Static and flow-through diffusion cells are both acceptable.
Sprejemljive so statične in pretočne difuzijske celice.
Normally, donor chambers are left unoccluded during exposure to a finite dose of a test preparation.
Običajno na donorskih komorah med izpostavljenostjo končnemu odmerku preskusnega pripravka ni okluzije.
However, for infinite applications and certain scenarios for finite doses, the donor chambers may be occluded.
Pri neprekinjenem nanašanju in pri določenih potekih pri končnih odmerkih pa je okluzija na na donorskih komorah lahko potrebna.
Receptor fluid
Receptorska tekočina
The use of a physiologically conducive receptor fluid is preferred although others may also be used provided that they are justified.
Uporaba fiziološko prevodne receptorske tekočine je bolj zaželena, čeprav se lahko uporabljajo tudi druge, če so utemeljene.
The precise composition of the receptor fluid should be provided.
Dana mora biti natančna sestava receptorske tekočine.
Adequate solubility of the test chemical in the receptor fluid should be demonstrated so that it does not act as a barrier to absorption.
Zagotovljena mora biti zadostna topnost preskusne kemikalije v receptorski tekočini, tako da ne deluje kot pregrada za absorpcijo.
In addition, the receptor fluid should not affect skin preparation integrity.
Poleg tega receptorska tekočina ne sme vplivati na neoporečnost kožnega pripravka.
In a flow-through system, the rate of flow must not hinder diffusion of a test substance into the receptor fluid.
V pretočnem sistemu hitrost pretoka ne sme ovirati difuzije preskusne snovi v receptorsko tekočino.
In a static cell system, the fluid should be continuously stirred and sampled regularly.
V sistemu statične celice je treba tekočino neprestano mešati in redno jemati vzorce.
If metabolism is being studied, the receptor fluid must support skin viability throughout the experiment.
Če se preučuje presnova, mora receptorska tekočina podpirati aktivnost kože med celotnim poskusom.
Skin preparations
Kožni pripravki
Although viable skin is preferred, non-viable skin can also be used provided that the integrity of the skin can be demonstrated.
Čeprav je bolj zaželena aktivna koža, se lahko uporablja tudi neaktivna koža, če je mogoče dokazati njeno neoporečnost.
Either epidermal membranes (enzymically, heat or chemically separated) or split thickness skin (typically 200-400 μm thick) prepared with a dermatome, are acceptable.
Sprejemljive so bodisi epidermalne membrane (encimsko, toplotno ali kemijsko ločene) ali koža z razcepljeno debelino (tipično debela 200-400 μm), pripravljena z dermatomom.
Full thickness skin may be used but excessive thickness (approximately > 1 mm) should be avoided unless specifically required for determination of the test chemical in layers of the skin.
Lahko se uporablja koža s celotno debelino, vendar se je treba izogibati prekomerni debelini (ca. > 1 mm), razen če je izrecno potrebna za določanje preskusnih kemikalij v plasteh kože.
The selection of species, anatomical site and preparative technique must be justified.
Izbira vrst, anatomsko mesto in tehnika pripravljanja morajo biti utemeljeni.
Acceptable data from a minimum of four replicates per test preparation are required.
Potrebni so sprejemljivi podatki iz najmanj štirih ponovitev na preskusni pripravek.
Skin preparation integrity
Neoporečnost kožnega pripravka
It is essential that the skin is properly prepared.
Bistveno je, da je koža pravilno pripravljena.
Inappropriate handling may result in damage to the stratum corneum, hence the integrity of the prepared skin must be checked.
Neustrezno ravnanje lahko poškoduje stratum corneum, zato je treba preveriti neoporečnost pripravljene kože.
When skin metabolism is being investigated, freshly excised skin should be used as soon as possible, and under conditions known to support metabolic activity.
Kadar se preiskuje presnova kože, je treba sveže izrezano kožo uporabiti čim hitreje in pod pogoji, ki podpirajo presnovno dejavnost.
As a general guidance, freshly excised skin should be used within 24 hours, but the acceptable storage period may vary depending on the enzyme system involved in metabolisation and storage temperatures (13).
Na splošno naj bo sveže izrezana koža uporabljena v 24 urah, sprejemljivo obdobje skladiščenja pa je lahko različno glede na encimski sistem presnavljanja in temperature skladiščenja (13).
When skin preparations have been stored prior to use, evidence should be presented to show that barrier function is maintained.
Če so kožni pripravki pred uporabo skladiščeni, je treba podati dokaze, ki izkazujejo ohranjanje pregradne funkcije.
The test substance preparation (e.g. neat, diluted or formulated material containing the test substance which is applied to the skin) should be the same (or a realistic surrogate) as that to which humans or other potential target species may be exposed.
Pripravek preskusne snovi (npr. čist, razredčen ali sestavljen material, ki vsebuje preskusno snov, ki se nanese na kožo) naj bo enak (ali realističen nadomestek) tistemu, kateremu so izpostavljeni ljudje ali druge možne ciljne vrste.
Any variation from the ‘in-use’ preparation must be justified.
Vsako odstopanje od pripravka, ki se uporablja v praksi, mora biti utemeljeno.
Test substances concentrations and formulations
Koncentracije in izdelave pripravkov preskusnih snovi
Normally more than one concentration of the test substance is used spanning the upper of potential human exposures.
Običajno se uporablja več kot ena koncentracija preskusne snovi, da zajema zgornjo možno izpostavljenost človeka.
Likewise, testing a range of typical formulations should be considered.
Enako je treba upoštevati razpon preskušanja značilnih pripravkov.
Under normal conditions of human exposure to chemicals, finite doses are usually encountered.
Pod normalnimi pogoji izpostavljenosti človeka kemikalijam gre ponavadi za končne odmerke.
Therefore, an application that mimics human exposure, normally 1-5 mg/cm2 of skin for a solid and up to10 μl/cm2 for liquids, should be used.
Zato je treba uporabiti nanos, ki oponaša izpostavljenost človeka, običajno 1-5 mg/cm2 kože za trdne snovi in do 10 μl/cm2 za tekočine.
The quantity should be justified by the expected use conditions, the study objectives or physical characteristics of the test preparation.
Količina mora biti utemeljena s pričakovanimi pogoji uporabe, cilji preučevanja ali fizičnimi lastnostmi preskusnega pripravka.
For example, applications to the skin surface may be infinite, where large volumes per unit area are applied.
Nanosi na površino kože so lahko, na primer, neprekinjeni, če se nanašajo veliki volumni na enoto površine.
The passive diffusion of chemicals (and therefore their skin absorption) is affected by temperature.
Na pasivno difuzijo kemikalij (in zato njihovo absorpcijo skozi kožo) vpliva temperatura.
The diffusion chamber and skin should be maintained at a constant temperature close to normal skin temperature of 32 ± 1 oC.
Difuzijsko komoro in kožo je treba ohranjati pri konstantni temperaturi, ki je blizu normalni temperature kože, to je 32 – 1 oC.
Different cell designs will require different water bath or heated block temperatures to ensure that the receptor/skin is at its physiological norm.
Različne oblike celic zahtevajo različne temperature vodne kopeli ali toplotnih blokov, da se zagotavlja fiziološka norma receptorja/kože.
Humidity should preferably be between 30 and 70 %.
Vlažnost naj bo po možnosti od 30 do 70 %.
Skin exposure to the test preparation may be for the entire duration of the experiment or for shorter times (i.e., to mimic a specific type of human exposure).
Koža je lahko izpostavljena preskusnemu pripravku med celotnim poskusom ali krajši čas (tj., zaradi oponašanja določene vrste izpostavljenosti človeka).
The skin should be washed of excess test preparation with a relevant cleansing agent, and the rinses collected for analysis.
S kože je treba z ustreznim čistilnim sredstvom izprati odvečni preskusni pripravek in preostanek zbrati za analizo.
The removal procedure of the test preparation will depend on the expected use condition, and should be justified.
Postopek odstranjevanja preskusnega pripravka je odvisen od pogoja pričakovane uporabe in ga je treba utemeljiti.
A period of sampling of 24 hours is normally required to allow for adequate characterisation of the absorption profile.
Običajno se zahteva obdobje vzorčenja 24 ur za omogočanje zadostne karakterizacije absorpcijskega profila.
Sampling frequency of the receptor fluid should allow the absorption profile of the test substance to be presented graphically.
Pogostost vzorčenja receptorske tekočine mora omogočati grafično predstavitev absorpcijskega profila preskusne snovi.
All components of the test system should be analysed and recovery is to be determined.
Vse elemente sistema preskusa je treba analizirati in določiti izkoristek.
This includes the donor chamber, the skin surface rinsing, the skin preparation and the receptor fluid/chamber.
To obsega donorsko komoro, izpiranje površine kože, kožni pripravek in receptorsko komoro/komoro s tekočino.
In some cases, the skin may be fractionated into the exposed area of skin and area of skin under the cell flange, and into stratum corneum, epidermis and dermis fractions, for separate analysis.
V nekaterih primerih se koža lahko frakcionira na izpostavljeno površino kože in površino kože pod celičnim robom ter na stratum corneum, epidermis in dermis fractions za ločeno analizo.
In all studies adequate recovery should be achieved (the aim should be a mean of 100±10 % of the radioactivity and any deviation should be justified).
Pri vseh študijah je treba doseči zadosten izkoristek (cilj bi moral biti povprečje 100 – +/-10 % radioaktivnosti in vsaka odstopanja morajo biti utemeljena).
The amount of test substance in the receptor fluid, skin preparation, skin surface washings and apparatus rinse should be analysed, using a suitable t echnique.
Količino preskusne snovi v receptorski tekočini, kožni pripravek, izpiranja s površine kože in kar se izpere z aparature je treba z ustrezno tehniko analizirati.
The analysis of receptor fluid, the distribution of the test substance chemical in the test system and the absorption profile with time, should be presented.
Predstaviti je treba analizo receptorske tekočine, distribucijo kemikalij preskusne snovi v sistemu preskusa in absorpcijski profil glede na čas.