natgillin/translations-raw huggingface dataset:
If necessary, a preliminary range finding study can be carried out with a few animals to select the appropriate dose groups [using methods for acute toxicity testing (Chapters B.1 bis, B.1 tris of this Annex (27), OECD TG 425 (19))].
Metodo humane usmrtitve je treba zabeležiti v laboratorijskem poročilu.
The objective in the case of the Hershberger Bioassay is to select doses that ensure animal survival and that are without significant toxicity or distress to the animals after 10 consecutive days of chemical administration up to a limit dose of 1000 mg/kg/d as noted in paragraphs 35 and 36.
Zaželen je naključni vrstni red obdukcije po skupinah, da ne bi prišlo do napredovanja neposredno po skupinah odmerkov, kar bi lahko vplivalo na podatke.
In this respect an OECD Guidance Document (17) may be used defining clinical signs indicative of toxicity or distress to the animals.
Vse ugotovitve pri obdukciji, tj. patološke spremembe/vidne poškodbe, je treba zabeležiti in o njih poročati.
If feasible within this range finding study after 10 days of administration, the target tissues may be excised and weighed approximately 24-hours after the last dose is administered.
Pet od androgenov odvisnih tkiv (VP, SV, LABC, COW, GP) je treba stehtati.
These data could then be used to assist the selection of the doses in the main study.
Ta tkiva je treba izrezati, previdno odstraniti priraščena tkiva in maščobo ter določiti njihovo svežo (nefiksirano) težo.
Reference chemicals and vehicle
Z vsakim tkivom je treba ravnati zelo skrbno, da ne bi prišlo do izgube tekočin in izsušitve, zaradi česar bi lahko prišlo do precejšnjih napak in variabilnosti, saj bi se zabeležene teže zmanjšale.
The reference androgen agonist should be Testosterone Propionate (TP), CAS No 57-82-5.
Več tkiv je lahko zelo majhnih ali pa jih je težko secirati, zaradi česar bo prišlo do variabilnosti.
The reference TP dosage may be either 0,2 mg/kg-bw/d or 0,4 mg/kg-bw/d.
Zato je pomembno, da osebe, ki secirajo tkiva pomožnih spolnih organov, poznajo standardne postopke seciranja za ta tkiva.
The reference androgen antagonist should be Flutamide (FT), CAS No 1311-84-7.
Priročnik s standardnim operativnim postopkom za seciranje je na voljo na spletni strani OECD (21).
The reference FT dosage should be 3 mg/kg-bw/d, and the FT should be co-administered with the reference TP dosage.
S skrbnim usposabljanjem v skladu s priročnikom s standardnim operativnim postopkom se bo zmanjšal morebitni vir variacij v študiji.
However, since many androgen 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).
Zaželeno je, da je za seciranje zadevnega tkiva zadolžen isti obducent, saj tako ne pride do razlik med posamezniki pri obdelavi tkiva.
The toxic characteristics of the solvent should be known, and should be tested in a separate solvent-only control group.
Če to ni mogoče, bi morala biti obdukcija zasnovana tako, da vsak obducent secira zadevno tkivo iz vseh tretiranih skupin, namesto da en posameznik secira vsa tkiva kontrolne skupine, nekdo drug pa je zadolžen za tretirane skupine.
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 using care to avoid contamination and spoilage of the samples.
Vsako tkivo pomožnega spolnega organa je treba stehtati brez pivnanja na 0,1 mg natančno in zabeležiti težo za vsako žival.
TP should be administered by subcutaneous injection, and FT by oral gavage.
Iz preteklega dela je razvidna vrsta koeficientov variacij, za katere se zdi, da se razlikujejo glede na strokovnost laboratorija.
Animal welfare considerations and the physical/chemical properties of the test chemical need to be taken into account when choosing the route of administration.
V nekaj primerih so bile v določenem laboratoriju ugotovljene velike razlike v absolutni teži tkiv, kot sta ventralna prostata in Cowperjevi žlezi.
In addition, 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) and existing toxicological information and data on metabolism and kinetics (e.g. need to avoid first pass metabolism, better efficiency via a particular route) should be taken into account before extensive, long-term testing is initiated if positive results are obtained by injection.
Lahko se opravijo tudi meritve jeter, obeh ledvic in obeh nadledvičnih žlez.
The animals should be dosed in the same manner and time sequence for 10 consecutive days at approximately 24 hour intervals.
S teh tkiv je prav tako treba odstraniti odvečno priraščeno vezivno tkivo in maščobo.
The dosage level should be adjusted daily based on the concurrent daily measures of body weight.
Jetra je treba stehtati in težo zabeležiti na 0,1 g natančno, prav tako je treba stehtati obe ledvici in nadledvični žlezi ter težo zabeležiti na 0,1 mg natančno.
The volume of dose and time that it is administered should be recorded on each day of exposure.
Lahko se opravijo tudi meritve serumskega luteinizirajočega hormona (LH), hormona, ki spodbuja rast foliklov (FSH), in testosterona (T).
Care should be taken in order not to exceed the maximum dose described in paragraph 35 to allow a meaningful interpretation of the data.
Koncentracije serumskega testosterona so koristne pri ugotavljanju, ali preskusna kemikalija povzroča presnovo testosterona v jetrih in tako znižuje koncentracije v serumu.
Reduction of body weight, clinical signs, and other findings should be thoroughly assessed in this respect.
Brez podatkov o testosteronu bi se lahko zdelo, da je do tega učinka prišlo zaradi antiandrogenega mehanizma.
For oral gavage, a stomach tube or a suitable intubation cannula should be used.
Koncentracije LH zagotavljajo informacije glede zmožnosti antiandrogena, da zmanjša težo organov in vpliva na funkcijo hipotalamusa in hipofize, ki lahko v dolgotrajnih študijah povzroči tumorje na modih.
For subcutaneous injections, doses should be administered to the dorsoscapular and or lumbar regions via sterile needle (e.g. 23- or 25-gauge) and a tuberculin syringe.
Hormon FSH je pomemben hormon za spermatogenezo.
The total volume injected per rat per day should not exceed 0,5 ml/kg body weight.
Lahko se opravijo tudi meritve T4 in T3 v serumu, ki bi zagotovile koristne dodatne informacije o zmožnosti za porušenje hormonskega ravnovesja ščitnice.
Specific procedures for androgen agonists
Če se bodo opravile meritve hormonov, je treba pred obdukcijo podgane omamiti in vzeti kri s punkcijo srca, metodo anestezije pa je treba skrbno izbrati, da ne bi vplivala na meritve hormonov.
For the test for androgen agonists, the vehicle is the negative control, and the TP-treated group is the positive control.
Metodo priprave seruma, vir radioimunskega preskusa ali druge komplete za merjenje, analitične postopke in rezultate je treba zabeležiti.
Biological activity consistent with androgen agonists is tested by administering a test chemical to treatment groups at the selected doses for 10 consecutive days.
Koncentracije LH je treba zabeležiti kot ng na ml seruma in testosteron je treba prav tako zabeležiti kot ng na ml seruma.
The weights of the five sex accessory tissues from the test chemical groups are compared to the vehicle group for statistically significant increases in weight.
Seciranje tkiv je opisano v nadaljevanju s podrobnim priročnikom za seciranje s fotografijami, ki so bile kot dodatno gradivo objavljene v okviru programa validacije (21).
Specific procedures for androgen antagonists and 5α-reductase inhibitors
Na spletni strani korejske uprave za hrano in zdravila je na voljo tudi posnetek seciranja (22).
For the test for androgen antagonists and 5α-reductase inhibitors, the TP-treated group is the negative control, and the group coadministered with reference doses of TP and FT is the positive control.
Žival je obrnjena z ventralno površino navzgor; preveriti je treba, ali se je kožica penisa ločila od glavice.
Biological activity consistent with androgen antagonists and 5α-reductase inhibitors is tested by administering a reference dose of TP and administering the test chemical for 10 consecutive days.
Če sta ločeni, je treba umakniti kožico in odstraniti glavico penisa, jo stehtati (na 0,1 mg natančno) in težo zabeležiti.
The weights of the five sex accessory tissues from the TP plus test chemical groups are compared to the reference TP-only group for statistically significant decreases in weights.
Kožo na trebuhu in trebušno steno je treba prerezati, s čemer se razkrijejo notranji organi.
Clinical observations
Če se bodo opravile meritve neobveznih organov, je treba odstraniti jetra in jih stehtati na 0,1 g natančno, odstraniti želodec in črevesje, odstraniti obe ledvici in nadledvični žlezi ter jih stehtati na 0,1 mg natančno.
All animals should 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).
S tem postopkom se razkrije mehur in začne seciranje tarčnih moških pomožnih organov.
Any animal found dead should be removed and disposed of without further data analysis.
Za seciranje ventralne prostate (VP) je treba mehur s prerezom veznega tkiva po sredini ločiti od plasti ventralnih mišic.
Any mortality of animals prior to necropsy should be included in the study record together with any apparent reasons for mortality.
Mehur je treba premakniti anteriorno proti semenskim mešičkom, da se razkrijeta levi in desni reženj ventralne prostate (prekrita s plastjo maščobe).
Any moribund animals should be humanely terminated.
Z desnega in levega režnja VP je treba previdno odstraniti maščobo.
Any moribund and subsequently euthanised animals should be included in the study record with apparent reasons for morbidity.
Desni reženj VP je treba previdno odmakniti od sečnice ter ločiti reženj in sečnico.
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.
Med držanjem desnega režnja VP je treba nežno odmakniti levi reženj VP in ga izrezati;
Dissection and measurement of tissue and organ weights
režnja je treba stehtati na 0,1 mg natančno in težo zabeležiti.
Approximately 24 hours after the last administration of the test chemical, the rats should be euthanised and exsanguinated according to the normal procedures of the conducting laboratory, and necropsy carried out.
Za seciranje semenskih mešičkov in koagulacijskih žlez je treba kavdalno premakniti mehur, s čemer se razkrijejo semenovod, desni in levi reženj semenskih mešičkov in koagulacijske žleze (SVCG).
The method of humane killing should be recorded in the laboratory report.
Treba je preprečiti uhajanje tekočine, in sicer tako, da se s sponko spne spodnji del SVCG, kjer se stikata semenovod in sečnica.
Ideally, the necropsy order should be randomised across groups to avoid progression directly up or down dose groups that could affect the data.
SVCG je treba previdno izrezati, s sponko še vedno na mestu odstraniti maščobo in priraščena tkiva, nato pa ju položiti v tarirano posodo za tehtanje, odstraniti sponko, stehtati organe na 0,1 mg natančno in težo zabeležiti.
Any finding at necropsy, i.e. pathological changes/visible lesions should be noted and reported.
Za seciranje mišice levator ani z bulbokavernozno mišico (LABC) je treba razkriti mišice in koren penisa.
The five androgen-dependent tissues (VP, SV, LABC, COW, GP) should be weighted.
Mišice LA so ovite okrog debelega črevesa, sprednje mišice LA in BC pa so pritrjene na čebulček penisa.
These tissues should be excised, carefully trimmed of excess adhering tissue and fat, and their fresh (unfixed) weights determined.
Odstraniti je treba kožo in adneks s perianalnega območja, ki potekata od korena penisa do sprednjega dela anusa.
Each tissue should be handled with particular care to avoid the loss of fluids and to avoid desiccation, which may introduce significant errors and variability by decreasing the recorded weights.
Postopoma je treba odstraniti mišice BC od čebulčka in tkiv.
Several of the tissues may be very small or difficult to dissect, and this will introduce variability.
Debelo črevo je treba prerezati na pol, nato pa se lahko v celoti izrežejo mišice LABC in odstranijo.
Therefore, it is important that persons carrying out the dissection of the sex accessory tissues are familiar with standard dissection procedures for these tissues.
Z mišic LABC je treba odstraniti maščobo in priraščena tkiva, nato pa mišice stehtati na 0,1 mg natančno in težo zabeležiti.
A standard operating procedure (SOP) manual for dissection is available from the OECD (21).
Ko so mišice LABC odstranjene, sta vidni okrogli Cowperjevi ali bulbouretralni žlezi (COW) pri spodnjem delu in nekoliko dorzalno od čebulčka.
If this is not possible, the necropsy should be designed such that each prosector dissects a given tissue from all treatment groups as opposed to one individual dissecting all tissues from a control group, while someone else is responsible for the treated groups.
Zabeležiti je treba tudi izgubo tekočine iz katere koli žleze med obdukcijo in seciranjem.
Each sex accessory tissues should be weighed without blotting to the nearest 0,1 mg, and the weights recorded for each animal.
Če je za oceno vsake kemikalije potrebna obdukcija večjega števila živali, kot je smiselno za en dan, se lahko začetek študije razporedi na dva zaporedna dneva, kar pomeni, da bo obdukcija in s tem povezano delo razporejeno na dva dneva.
Previous work has indicated a range of coefficient of variations (CVs) that appears to differ based upon the proficiency of the laboratory.
V tem primeru je treba uporabiti polovico živali vsake od tretiranih skupin na dan.
In a few cases, large differences in the absolute weights of the tissues such as the VP and COWS have been observed within a particular laboratory.
Po obdukciji je treba trupla uničiti na primeren način.
Liver, paired kidney, and paired adrenal weights are optional measurements.
POROČANJE
Again, tissues should be trimmed free of any adhering fascia and fat.
Podatki se sporočajo posamično (tj. telesna teža, teža tkiva pomožnih spolnih organov, neobvezne meritve ter drugi odzivi in opažanja) in za vsako skupino živali (srednji in standardni odkloni vseh meritev).
The liver should be weighed and recorded to the nearest 0,1 g and the paired kidneys and paired adrenals should be weighed and recorded to the nearest 0,1 mg.
Podatki se povzamejo v obliki tabele.
The liver, kidney and adrenals are not only influenced by androgens;
Podatki prikazujejo število živali na začetku preskusa, število živali, najdenih poginulih ali najdenih, ko kažejo znake strupenosti med preskusom, opis znakov zaznane strupenosti, vključno s časom njenega začetka, trajanja in resnosti.
they also provide useful indices of systemic toxicity.
Končno poročilo mora vključevati naslednje podatke:
Measurement of serum luteinising hormone (LH), follicular stimulating hormone (FSH) and testosterone (T) is optional.
Preskuševalni laboratorij:
Serum T levels are useful to determine if the test chemical induces liver metabolism of testosterone, lowering serum levels.
naziv laboratorija, kraj,
Without the T data, such an effect might appear to be via an antiandrogenic mechanism.
vodjo študije in drugo osebje ter njegove pristojnosti v zvezi s študijo,
LH levels provides information about the ability of an antiandrogen to not only reduce organ weights, but also to affect hypothalamic-pituitary function, which in long term studies can induce testis tumors.
datume začetka in konca študije, tj. prvi dan dajanja preskusne kemikalije oziroma zadnji dan obdukcije.
FSH is an important hormone for spermatogenesis.
Preskusna kemikalija
Serum T4 and T3 also are optional measures that would provide useful supplemental information about the ability to disrupt thyroid hormone homeostasis.
izvor, številko serije, vrsto, čistoto, polni naslov dobavitelja in opredelitev preskusnih kemikalij,
If hormone measurements are to be made, the rats should be anesthetised prior to necropsy and blood taken by cardiac puncture, and the method of anaesthesia should be chosen with care so that it does not affect hormone measurement.
agregatno stanje in, če je to ustrezno, fizikalno-kemijske lastnosti,
The method of serum preparation, the source of radioimmunoassay or other measurement kits, the analytical procedures, and the results should be recorded.
pogoje shranjevanja, metodo in pogostost priprave razredčin,
LH levels should be reported as ng per ml of serum, and T should also be reported as ng per ml of serum.
morebitne analize raztopin/suspenzij za odmerjanje.
The dissection of the tissues is described as follows with a detailed dissection guide with photographs published as supplementary materials as part of the validation programme (21).
Nosilec:
A dissection video is also available from the Korea Food and Drug Administration web page (22).
opredelitev nosilca (vrsta, dobavitelj in št. serije),
With the ventral surface of the animal upwards, determine if the prepuce of the penis has separated from the glans penis.
utemeljitev izbire nosilca (če ta ni voda).
If so, then retract the prepuce and remove the glans penis, weigh (nearest 0,1 mg), and record the weight;
Preskusne živali in postopki reje živali:
Open the abdominal skin and wall, exposing the viscera.
uporabljeno vrsto/sev in utemeljitev izbire,
If the optional organs are weighed, remove and weigh liver to nearest 0,1 g, remove the stomach and intestines, remove and weigh the paired kidneys and paired adrenals to the nearest 0,1 mg.
izvor ali dobavitelja živali, vključno s polnim naslovom,
This dissection exposes the bladder and begins the dissection of the target male accessory tissues.
število in starost dobavljenih živali,
To dissect the VP, separate bladder from the ventral muscle layer by cutting connective tissue along the midline.
pogoje nastanitve (temperaturo, osvetlitev itd.),
Displace the bladder anteriorly towards the seminal vesicles (SV), revealing the left and right lobes of the ventral prostate (covered by a layer of fat).
prehrano (ime, vrsto, dobavitelja, št. serije, vsebino in, če so znane, ravni fitoestrogenov),
Carefully tease the fat from the right and left lobes of the VP.
pogoje v kletkah in število živali na posamezno kletko.
Gently displace the VP right lobe from the urethra and dissect the lobe from the urethra.
Preskusni pogoji:
While still holding the VP right lobe, gently displace the VP left lobe from the urethra and then dissect;
starost ob kastraciji in trajanje prilagajanja po kastraciji,
weigh to nearest 0,1 mg and record the weight.
teže posameznih živali ob začetku študije (na 0,1 g natančno),
To dissect the SVCG, displace the bladder caudally, exposing the vas deferens and right and left lobes of the seminal vesicles plus coagulating glands (SVCG).
postopek randomizacije in evidenco dodelitve v skupine z nosilcem, referenčne skupine, skupine, ki so prejele preskusno kemikalijo, in kletke,
Prevent leakage of fluid by clamping a haemostat at the base of the SVCGs, where the vas deferens joins the urethra.
srednji in standardni odklon telesne teže za vsako skupino za vsak dan tehtanja v času trajanja študije,
Carefully dissect the SVCGs, with the haemostat in place trim fat and adnexa away, place in a tared weigh-boat, remove the haemostat, and weigh to the nearest 0,1 mg and record the weight.
način dajanja preskusne kemikalije in utemeljitev izbire načina izpostavljenosti,
To dissect the levator ani plus bulbocavernosus muscles (LABC), the muscles and the base of the penis are exposed.
če je bil opravljen preskus za antiandrogenost, tretiranje s TP (odmerek in količino),
The LA muscles wrap around the colon, while the anterior LA and BC muscles are attached to the penile bulbs.
tretiranje s preskusno kemikalijo (odmerek in količina),
The skin and adnexa from the perianal region extending from the base of the penis to the anterior end of the anus are removed.
čas odmerjanja,
The BC muscles are gradually dissected from the penile bulb and tissues.
postopke obdukcije, vključno z načini izkrvavitve in morebitne anestezije,
The colon is cut in two and, the full LABC can be dissected and removed.
če so bile opravljene analize seruma, podrobnosti metode.
The LABC should be trimmed of fat and adnexa, weighed to the nearest 0,1 mg, and record the weight.
Če je bil na primer uporabljen radioimunski preskus (RIA), je treba sporočiti izvor kompletov za izvedbo preskusa, datum poteka kompleta, postopek scintilacijskega štetja in standardiziranje.
After the LABC has been removed, the round Cowper's or bulbourethral glands (COW) are visible at the base of, and slightly dorsal to, the penile bulbs.
dnevna opazovanja za vsako žival med dajanjem odmerkov, vključno s:
Careful dissection is required to avoid nicking the thin capsule in order to prevent fluid leakage.
telesno težo (na 0,1 g natančno),
Weigh the paired COW to the nearest 0,1 mg, and record the weight.
kliničnimi znaki (če se pojavijo),
In addition, if fluid is lost from any gland during the necropsy and dissection, this should be recorded.
morebitnimi meritvami ali opombami o porabi hrane,
If the evaluation of each chemical requires necropsy of more animals than is reasonable for a single day, the study start may be staggered on two consecutive days, resulting in the staggering of the necropsy and the related work over two days.
opazovanja pri obdukciji za vsako žival, vključno z:
If staggered in this manner,one-half of the animals per treatment group should be used per day.
datumom obdukcije,
Carcasses should be disposed of in an appropriate manner following necropsy.
skupino tretiranja živali,
REPORTING
identifikacijsko oznako živali,
Data should be reported individually (i.e. body weight, accessory sex tissue weights, optional measurements and other responses and observations) and for each group of animals (means and standard deviations of all measurement taken).
obducentom,
The data should be summarised in tabular form.
časom dneva, ko sta bili opravljeni obdukcija in seciranje,
The data should show the number of animals at the start of the test, the number of animals found dead during the test or found showing signs of toxicity, a description of the signs of toxicity observed, including time of onset, duration and severity.
starostjo živali,
A final report should include:
končno telesno težo pri obdukciji in zabeleženo morebitno statistično značilno povečanje ali zmanjšanje,
Testing facility
vrstnim redom izkrvavitve živali in seciranja pri obdukciji,
Name of facility, location
težo petih tarčnih od androgenov odvisnih tkiv:
Study director and other personnel and their study responsibilities
ventralne prostate (na 0,1 mg natančno),
Dates the study began and ended, i.e. first day of test chemical administration and last day of necropsy, respectively.
semenskih mešičkov in koagulacijskih žlez, skupaj s tekočino (obeh, na 0,1 mg natančno),
Test chemical
sistema mišice levator ani z bulbokavernozno mišico (na 0,1 mg natančno),
Source, lot/batch number, identity, purity, full address of the supplier and characterisation of the test chemical(s)
Cowperjevih žlez (sveža teža – obeh, na 0,1 mg natančno),
Physical nature and, where relevant, physicochemical properties;
glavice penisa (sveža teža, na 0,1 mg natančno),
Storage conditions and the method and frequency of dilution preparation
morebitno težo neobveznih tkiv:
Any analyses of dosing solutions/suspensions.
jeter (na 0,1 g natančno),
Vehicle
ledvic (obeh, na 0,1 mg natančno),
Characterisation of the vehicle (identity, supplier and lot #)
nadledvičnih žlez (obeh, na 0,1 mg natančno),
Justification of the vehicle choice (if other than water)
splošne pripombe in komentarje.
Test animals and animal husbandry procedures
morebitne analize serumskih hormonov:
Species/strain used and rationale for choice
serum LH (ni obvezno – ng na ml seruma) in