natgillin/translations-raw huggingface dataset:
These data could then be used to assist the main study design (select an acceptable maximum and lower doses and recommend the number of dose groups).
Podgane so humano usmrčene 24 ur po prejetem zadnjem odmerku.
The test chemical is administered by oral gavage or subcutaneous injection.
Zaželen je naključni vrstni red obdukcije po skupinah, da ne bi prišlo do napredovanja neposredno po skupinah odmerkov, kar bi lahko v manjši meri vplivalo na podatke.
Animal welfare considerations as well as toxicological aspects like the relevance to the human route of exposure to the chemical (e.g. oral gavage to model ingestion, subcutaneous injection to model inhalation or dermal adsorption), the physical/chemical properties of the test material and especially existing toxicological information and data on metabolism and kinetics (e.g. need to avoid first pass metabolism, better efficiency via a particular route) have to be taken into account when choosing the route of administration.
Cilj biološkega preskusa je merjenje teže mokre in osušene maternice.
It is recommended that, wherever possible, the use of an aqueous solution/suspension be considered first.
V mokri teži je zajeta maternica s tekočinami v lumnu.
But as most oestrogen ligands or their metabolic precursors tend to be hydrophobic, the most common approach is to use a solution/suspension in oil (e.g. corn, peanut, sesame or olive oil).
Osušena teža se izmeri po odstranitvi tekočin v lumnu maternice.
However, these oils have different caloric and fat content, thus the vehicle might affect total metabolisable energy (ME) intake, thereby potentially altering measured endpoints such as the uterine weight especially in the immature method (33).
Pred seciranjem je treba pri nezrelih živalih preveriti odpiranje nožnice.
Thus, prior to the study, any vehicle to be used should be tested against controls without vehicles.
Postopek seciranja se začne s prerezom trebušne stene pri sramnični zrasti.
Test chemicals can be dissolved in a minimal amount of 95 % ethanol or other appropriate solvents and diluted to final working concentrations in the test vehicle.
Nato je treba rog maternice in jajčnike, če so prisotni, ločiti od dorzalne trebušne stene.
The toxic characteristics of the solvent must be known, and should be tested in a separate solvent-only control group.
Sečni mehur in uretri je treba odstraniti z ventralne in lateralne strani maternice in nožnice.
If the test chemical is considered stable, gentle heating and vigorous mechanical action can be used to assist in dissolving the test chemical.
Brazgotinasto zarastlino med rektumom in nožnico je treba ločiti tako, da je viden stik nožničnega ustja in presredka.
The stability of the test chemical in the vehicle should be determined.
Maternico in nožnico se od telesa loči s prerezom nožnične stene tik nad stikom s presredkom, kot je prikazano na sliki 2.
If the test chemical is stable for the duration of the study, then one starting aliquot of the test chemical may be prepared, and the specified dosage dilutions prepared daily.
Maternico je treba od telesne stene ločiti s previdnim prerezom mezenterija maternice od točke pritrditve po celotni dorzolateralni dolžini vsakega roga maternice.
Dosage timing will depend of the model used (refer to paragraph 29 for the immature model and to paragraph 30 for ovx-adult model).
Po odstranitvi maternice iz telesa je treba biti dovolj hiter, da ne pride do izsušitve tkiv.
Immature female rats are dosed with the test chemical daily for three consecutive days.
Izguba teže zaradi izsušitve je pomembnejša pri majhnih tkivih, kot je maternica (23).
A three-day treatment is also recommended for ovariectomised female rats but longer exposures are acceptable and may improve the detection of weakly active chemicals.
Če so jajčniki prisotni, jih je treba ločiti pri jajcevodu in paziti, da ne pride do izgube tekočine iz lumna roga maternice.
With ovariectomised female mice, an application duration of 3 days should be sufficient without a significant advantage by an extension of up to seven days for strong oestrogen agonists, however, this relation was not demonstrated for weak oestrogens in the validation study (16) thus dosage should be extended up to 7 consecutive days in ovx-adult mice.The dose should be given at similar times each day.
Če je bila žival sterilizirana, je treba ostanke jajčnikov pregledati zaradi morebitne prisotnosti tkiva jajčnikov.
They should be adjusted as necessary to maintain a constant dose level in terms of animal body weight (e.g. mg of test chemical per kg of body weight per day).
Odstraniti je treba odvečno maščobo in vezno tkivo.
Regarding the test volume, its variability, on a body weight basis, should be minimised by adjusting the concentration of the dosing solution to ensure a constant volume on a body weight basis at all dose levels and for any route of administration.
Nožnico je treba od maternice ločiti tik pod materničnim vratom, tako da vrat ostane pritrjen na maternico, kot je prikazano na sliki 2.
When the test chemical is administered by gavage, this should be done in a single daily dose to the animals using a stomach tube or a suitable intubation cannula.
Maternice je treba posamično prenesti v edinstveno označeno in stehtano posodo (npr. petrijevko ali plastično posodo za tehtanje), pri čemer je treba še vedno paziti, da pred tehtanjem ne pride do izsušitve (npr. v posodo se lahko na primer odloži filtrirni papir, rahlo navlažen z raztopino vode in soli).
The maximum volume of liquid that can be administered at one time depends on the size of the test animal.
Maternico s tekočino v lumnu se stehta na 0,1 mg natančno (mokra teža maternice).
Local animal care guidelines should be followed, but the volume should not exceed 5 ml/kg body weight, except in the case of aqueous solutions where 10 ml/kg body weight may be used.
Vsako posamezno maternico je treba nato posamično obdelati in odstraniti tekočino iz lumna.
When the test chemical is administered by subcutaneous injection, this should be done in a single daily dose.
Oba roga maternice se vzdolžno prebodeta ali prerežeta.
Doses should be administered to the dorsoscapular or lumbar regions via sterile needle (e.g. 23- or 25-gauge) and a tuberculin syringe.
Maternica se odloži na rahlo navlažen filtrirni papir (npr. Whatman št. 3) in nežno stisne z drugim kosom rahlo navlaženega filtrirnega papirja, da se popolnoma odstrani tekočina iz lumna.
Shaving the injection site is optional.
Maternica brez tekočine iz lumna se stehta na 0,1 mg natančno (osušena teža maternice).
Any losses, leakage at the injection site or incomplete dosing should be recorded.
S podatki o teži maternice ob usmrtitvi se je mogoče prepričati, da primerna starost nezrele nesterilizirane podgane ni bila presežena, vendar so glede tega odločilni pretekli podatki o sevu podgan, ki ga je uporabil laboratorij (glej odstavek 56 za razlago rezultatov).
The total volume injected per rat per day should not exceed 5 ml/kg body weight, divided into 2 injection sites, except in the case of aqueous solutions where 10 ml/kg body weight may be used.
Neobvezne preiskave
Observations
Po tehtanju se lahko maternica fiksira v 10-odstotnem nevtralnem formalinskem pufru in se po barvanju s hematoksilinom in eozinom histopatološko pregleda.
General and clinical observations
Skladno s tem se lahko pregleda tudi nožnica (glej odstavek 9).
General clinical observations should be made at least once a day and more frequently when signs of toxicity are observed.
Poleg tega se lahko za kvantitativno primerjavo opravi tudi morfometrično merjenje povrhnjice endometrija.
Observations should be carried out preferably at the same time(s) each day and considering the period of anticipated peak effects after dosing.
Podatki študije morajo obsegati:
All animals are to be observed for mortality, morbidity and general clinical signs such as changes in behaviour, skin, fur, eyes, mucous membranes, occurrence of secretions and excretions and autonomic activity (e.g. lacrimation, piloerection, pupil size, unusual respiratory pattern).
število posameznih živali na začetku preskusa,
Body weight and food consumption
število in identiteto živali, najdenih poginulih med preskusom ali usmrčenih iz humanih razlogov ter datum in čas pogina ali humane usmrtitve,
All animals should be weighed daily to the nearest 0,1 g, starting just prior to initiation of treatment i.e. when the animals are allocated into groups.
število in identiteto živali, ki kažejo znake strupenosti in opis znakov zaznane strupenosti, vključno s časom začetka, trajanja in resnosti morebitnih strupenih učinkov, in
As an optional measurement, the amount of food consumed during the treatment period may be measured per cage by weighing the feeders.
število in identiteto živali, pri katerih so vidne poškodbe, ter opis vrste poškodb.
The food consumption results should be expressed in grams per rat per day.
Zabeležiti je treba podatke za posamezne živali, in sicer njihovo telesno težo, mokro težo maternice ter osušeno težo maternice.
Dissection and measurement of uterus weight
Za ugotavljanje, ali se je zaradi odmerjanja preskusne kemikalije teža maternice statistično značilno povečala (p < 0,05), je treba uporabiti enostranske statistične analize za agoniste.
Twenty-four hours after the last treatment, the rats will be humanely killed.
Izvesti je treba ustrezne statistične analize za ugotavljanje sprememb v osušeni in mokri teži maternice zaradi prejemanja odmerkov.
Ideally, the necropsy order will be randomised across groups to avoid progression directly up or down dose groups that could subtly affect the data.
Podatki se lahko na primer ovrednotijo z analizo kovariance (ANCOVA), pri čemer je telesna teža pri obdukciji kovariat.
The bioassay objective is to measure both the wet and blotted uterus weights.
Pred analizo podatkov se lahko za podatke o maternici izvede logaritemska pretvorba podatkov za stabilizacijo varianc.
The wet weight includes the uterus and the luminal fluid contents.
Dunnettov in Hsujev preskus sta primerna za primerjave po parih vsake skupine, ki je prejela odmerek, s kontrolnimi vzorci, ki so prejemali le nosilec, in izračun intervalov zaupanja.
The blotted weight is measured after the luminal contents of the uterus have been expressed and removed.
Grafi studentiziranih ostankov se lahko uporabijo za odkrivanje morebitnih osamelcev in oceno homogenosti varianc.
Before dissection the vagina will be examined for opening status in immature animals.
Ti postopki so bili uporabljeni v programu OECD za validacijo z metodo PROC GLM v sistemu za statistično analizo (SAS Institute, Cary, Severna Karolina, ZDA), različica 8 (6) (7).
The dissection procedure begins by opening the abdominal wall starting at the pubic symphysis.
Končno poročilo mora vključevati naslednje podatke:
Then, uterine horn and ovaries, if present, are detached from the dorsal abdominal wall.
Preskuševalni laboratorij:
The urinary bladder and ureters are removed from the ventral and lateral side of uterus and vagina.
pristojno osebje in njihove pristojnosti v zvezi s študijo,
Fibrous adhesion between the rectum and the vagina is detached until the junction of vaginal orifice and perineal skin can be identified.
podatke preskusa osnovne pozitivne kontrole in periodične podatke o pozitivni kontroli (glej odstavka 26 in 27).
The uterus and vagina are detached from the body by incising the vaginal wall just above the junction between perineal skin as shown in Figure 2.
opredelitev preskusnih kemikalij,
The uterus should be detached from the body wall by gently cutting the uterine mesentery at the point of its attachment along the full length of the dorsolateral aspect of each uterine horn.
agregatno stanje in, če je to ustrezno, fizikalno-kemijske lastnosti,
Once removed from the body, uterine handling should be sufficiently rapid to avoid desiccation of the tissues.
metodo in pogostost priprave razredčin,
Loss of weight due to desiccation becomes more important with small tissues such as the uterus (23).
morebitne podatke o stabilnosti,
If ovaries are present, the ovaries are removed at the oviduct avoiding loss of luminal fluid from the uterine horn.
morebitne analize raztopin za odmerjanje.
If the animal has been ovariectomised, the stubs should be examined for the presence of any ovarian tissue.
Nosilec:
Excess fat and connective tissue should be trimmed away.
opredelitev nosilca (stanje, dobavitelj in št. serije),
The vagina is removed from the uterus just below the cervix so that the cervix remains with the uterine body as shown in Figure 2.
utemeljitev izbire nosilca (če ta ni voda).
Each uterus should be transferred to a uniquely marked and weighed container (e.g. a petri-dish or plastic weight boat) with continuing care to avoid desiccation before weighing (e.g. filter paper slightly dampened with saline may be placed in the container).
vrsto in sev ter utemeljitev izbire,
The uterus with luminal fluid will be weighed to the nearest 0,1 mg (wet uterine weight).
dobavitelja in določeni objekt dobavitelja,
Each uterus will then be individually processed to remove the luminal fluid.
starost ob dobavi z datumom kotitve,
Both uterine horns will be pierced or cut longitudinally.
pri nezrelih živalih podatek, ali so prispele skupaj z materami ali nadomestnimi materami, in datum odstavitve,
The uterus will be placed on lightly moistened filter paper (e.g. Whatman No 3) and gently pressed with a second piece of lightly moistened filter paper to completely remove the luminal fluid.
podrobnosti postopka prilagajanja živali,
The uterus without the luminal contents will be weighed to the nearest 0,1 mg (blotted uterine weight).
število živali na posamezno kletko,
The uterus weight at termination can be used to ensure that the appropriate age in the immature intact rat was not exceeded, however, the historical data of the rat strain used by the laboratory are decisive in this respect (see paragraph 56 for interpretation of the results).
podrobnosti in metodo edinstvenih oznak živali in skupin.
Optional investigations
Preskusni pogoji:
After weighing, the uterus may be fixed in 10 % neutral buffered formalin to be examined histopathologically after Haematoxylin & Eosin (HE)-staining.
podrobnosti postopka randomizacije (tj. uporabljenega postopka),
The vagina may be investigated accordingly (see paragraph 9).
utemeljitev izbire odmerka,
In addition, morphometric measurement of endometrial epithelium may be done for quantitative comparison.
podrobne podatke o formulaciji preskusne kemikalije, njeni doseženi koncentraciji, stabilnosti in homogenosti,
Study data should include:
podrobne podatke o dajanju preskusne kemikalije in utemeljitev izbire načina izpostavljenosti,
the number of animals at the start of the assay,
prehrano (ime, vrsto, dobavitelja, vsebino in, če so znane, ravni fitoestrogenov),
the number and identity of animals found dead during the assay or killed for humane reasons and the date and time of any death or humane kill,
izvor vode (npr. voda iz pipe ali filtrirana voda) in njena dobava (pretakanje iz velike posode, v steklenicah itd.),
the number and identity of animals showing signs of toxicity, and a description of the signs of toxicity observed, including time of onset, duration, and severity of any toxic effects, and
steljo (ime, vrsto, dobavitelja, vsebino),
the number and identity of animals showing any lesions and a description of the type of lesions.
evidenco o pogojih v kletkah, intervalih osvetlitve, sobni temperaturi in vlažnosti, čiščenju prostora,
Individual animal data should be recorded for the body weights, the wet uterine weight, and the blotted uterine weight.
podroben opis postopka obdukcije in tehtanja maternice,
One-tailed statistical analyses for agonists should be used to determine whether the administration of a test chemical resulted in a statistically significant (p < 0,05) increase in the uterine weight.
opis statističnih podatkov.
Appropriate statistical analyses should be carried out to test for treatment related changes in blotted and wet uterine weight.
Rezultati:
For example, the data may be evaluated by an analysis of covariance (ANCOVA) approach with body weight at necropsy as the co-variable.
Za posamezne živali:
A variance-stabilising logarithmic transformation may be carried out on the uterine data prior to the data analysis.
vse dnevne telesne teže posameznih živali (od dodelitve v skupine do obdukcije) (na 0,1 g natančno),
Dunnett and Hsu's test are appropriate for making pair wise comparisons of each dosed group to vehicle controls and to calculate the confidence intervals.
starost vsake posamezne živali (v dneh, pri čemer je dan skotitve dan 0) ob pričetku dajanja preskusne kemikalije,
Studentised residual plots can be used to detect possible outliers and to assess homogeneity of variances.
datum in čas dajanja vsakega odmerka,
These procedures were applied in the OECD validation programme using the PROC GLM in the Statistical Analysis System (SAS Institute, Cary, NC), version 8 (6)(7).
izračunani volumen in dan odmerek ter opažanja glede morebitne izgube odmerka med dajanjem odmerka ali po njem,
A final report shall include:
dnevno evidenco stanja živali, vključno z zadevnimi simptomi in opažanji,
Testing facility:
domnevni vzrok pogina (če je žival med študijo najdena umirajoča ali poginula),
Responsible personnel and their study responsibilities
datum in čas humane usmrtitve z navedbo časa, preteklega od zadnjega odmerka,
Data from the Baseline Positive Control Test and periodic positive control data (see paragraphs 26 and 27)
mokro težo maternice (na 0,1 mg natančno) ter morebitna opažanja glede izgube tekočine iz lumna med seciranjem in pripravo na tehtanje,
Characterisation of test chemicals
osušeno težo maternice (na 0,1 mg natančno).
Physical nature and where relevant physicochemical properties
Za vsako skupino živali:
Method and frequency of preparation of dilutions
srednje dnevne telesne teže (na 0,1 g natančno) in standardne odklone (od dodelitve v skupine do obdukcije),
Any data generated on stability
srednje mokre teže maternic in povprečne osušene teže maternic (na 0,1 mg natančno) in standardne odklone,
Any analyses of dosing solutions
če je izmerjena, dnevno porabo hrane (izračunano kot grami porabljene hrane na žival),
Vehicle:
rezultate statističnih analiz, ki primerjajo mokre in osušene teže maternic tretiranih skupin glede na enake meritve v kontrolnih skupinah z nosilcem,
Characterisation of test vehicle (nature, supplier and lot)
rezultate statističnih analiz, ki primerjajo skupno telesno težo in pridobljeno težo tretiranih skupin glede na enake meritve v kontrolnih skupinah z nosilcem.
Justification of choice of vehicle (if other than water)
Povzetek pomembnih smernic preskusne metode
Species and strain and justification for their choice
Podgana
Supplier and specific supplier facility
Živali
Age on supply with birth date
Sev
If immature animals, whether or not supplied with dam or foster dam and date of weaning
Običajno uporabljeni laboratorijski sevi glodavcev
Details of animal acclimatisation procedure
Število živali
Number of animals per cage
Najmanj 6 živali na skupino odmerka
Detail and method of individual animal and group identification
Število skupin
Assay Conditions:
Najmanj 2 preskusni skupini (za navodila glej odstavek 33) in negativna kontrolna skupina
Details of randomisation process (i.e. method used)
Za navodila glede pozitivnih kontrolnih skupin glej odstavka 26 in 27
Rationale for dose selection
T° v prostoru z živalmi
Details of test chemical formulation, its achieved concentrations, stability and homogeneity
22 °C ± 3 °C
Details of test chemical administration and rationale for the choice of exposure route
Relativna vlažnost
Diet (name, type, supplier, content, and, if known, phyto-oestrogen levels)
50–60 % in ne manj kot 30 % ali več kot 70 %
Water source (e.g. tap water or filtered water) and supply (by tubing from a large container, in bottles, etc.)
Dnevno zaporedje osvetlitve
Bedding (name, type, supplier, content)
12 ur svetlobe, 12 ur teme
Record of caging conditions, lighting interval, room temperature and humidity, room cleaning
Prehrana in pitna voda
Detailed description of necropsy and uterine weighing procedures
Nastanitev
Description of statistical procedures
Posamično ali v skupinah po največ tri živali (pri nezrelih živalih se priporoča družabna skupinska nastanitev)
Results
Prehrana in stelja
For individual animals:
Za prehrano in steljo priporočena nizka raven fitoestrogenov
All daily individual body weights (from allocation into groups through necropsy) (to the nearest 0,1 g)
Protokol
Age of each animal (in days counting day of birth as day 0) when administration of test chemical begins
Metoda
Date and time of each dose administration
Metoda z nezrelo nesterilizirano samico (zaželena)
Calculated volume and dosage administered and observations of any dosage losses during or after administration
Metoda s sterilizirano odraslo samico
Daily record of status of animal, including relevant symptoms and observations
Starost nezrelih živali ob odmerjanju
Suspected cause of death (if found during study in moribund state or dead)
Ne prej kot 18. poporodni dan.
Date and time of humane killing with time interval to last dosing
Dajanje odmerkov je treba zaključiti pred 25. poporodnim dnem.
Wet uterine weight (to the nearest 0,1 mg) and any observations of luminal fluid losses during dissection and preparation for weighing
V okviru področja uporabe obstoječe preskusne metode ni relevantna.
Blotted uterine weight (to the nearest 0,1 mg)
Starost ob sterilizaciji
Mean daily body weights (to the nearest 0,1 g) and standard deviations (from allocation into groups through necropsy)
Starost steriliziranih živali ob odmerjanju
Mean wet uterine weights and mean blotted uterine weights (to the nearest 0,1 mg) and standard deviations
Od sterilizacije do prvega dne dajanja odmerka bi moralo preteči vsaj 14 dni.
If measured, daily food consumption (calculated as grams of food consumed per animal)
Od sterilizacije do prvega dne dajanja odmerka bi moralo preteči vsaj 7 dni.
The results of statistical analyses comparing both the wet and blotted uterine weights of treated groups relative to the same measures in the vehicle control groups.
Nihanje telesne teže naj bo čim manjše in naj ne preseže ± 20 % srednje teže.
The results of statistical analysis comparing the total body weight and the body weight gain of treated groups relative to the same measures in the vehicle control groups.
Odmerjanje
Summary of the important guidance facts of the test method
Način dajanja kemikalije
Rat
Oralno z gavažo ali s podkožnim injiciranjem
Mice
Pogostost dajanja
Animals
Enkratni dnevni odmerek
Strain
Prostorninski delež za gavažo in injiciranje
Commonly used laboratory rodent strain
≤ 5 ml/kg telesne teže (ali do največ 10 ml/kg telesne teže pri vodnih raztopinah) (na dveh mestih injiciranja pri dajanju podkožno)
Number of animals
Trajanje odmerjanja
A minimum of 6 animals per dose group
3 zaporedne dni pri modelu z nezrelo samico
Number of groups
Najmanj 3 zaporedne dni pri modelu s sterilizirano odraslo samico
A minimum of 2 test groups (see paragraph 33 for guidance) and a negative control group
7 zaporednih dni pri modelu s sterilizirano odraslo samico
For guidance on positive control groups see paragraphs 26 and 27
Čas obdukcije
T° in animal room
Približno 24 ur po zadnjem odmerku
22 °C ± 3 °C
Pozitiven odziv
Relative humidity
Statistično značilno povečanje povprečne teže maternice (mokre in/ali osušene)
50-60 % and not below 30 % or above 70 %
Referenčni estrogen
Daily lighting sequence
etinilestradiol
12 hours light, 12 hours dark
SMERNICE ZA RAZLAGO IN PRIZNAVANJE REZULTATOV
Diet and drinking water
Na splošno se lahko preskus za estrogenost šteje za pozitivnega, če vsaj pri največjem odmerku pride do statistično značilnega povečanja teže maternice (p < 0,05) v primerjavi s kontrolno skupino, pri kateri je uporabljeno le topilo.
Housing
Pozitiven rezultat je nadalje podprt s prikazom biološko verjetnega razmerja med odmerkom in stopnjo odziva ob upoštevanju, da lahko estrogene in antiestrogene dejavnosti preskusne kemikalije, ki se prekrivajo, vplivajo na obliko krivulje odziva na odmerek.