natgillin/translations-raw huggingface dataset:
With respect to the latter, these are provisionally included.
U pogledu ovih drugih, oni su uključeni privremeno.
Once developed and validated, they will be formally added to the framework.
Nakon što budu razvijeni i validirani bit će formalno dodani u okvir.
Level 5 should not be considered as including definitive tests only.
Ne treba smatrati da razina 5. obuhvaća samo definitivne testove.
Tests included at that level are considered to contribute to general hazard and risk assessment.
Smatra se da testovi uključeni na toj razini doprinose općoj procjeni opasnosti i rizika.
OECD Environmental Health and Safety Publication Series on Testing and Assessment No 38.
OECD Environmental Health and Safety Publication Series on Testing and Assessment No. 38.
OECD Environmental Health and Safety Publication Series on Testing and Assessment No 65.
OECD Environmental Health and Safety Publication Series on Testing and Assessment No. 65.
OECD Environmental Health and Safety Publication Series on Testing and Assessment No 66.
OECD Environmental Health and Safety Publication Series on Testing and Assessment No. 66.
The postnatal ontogeny of rat uterine glands and age-related effects of 17b-estradiol.
The postnatal ontogeny of rat uterine glandsand age-related effects of 17β-estradiol.
OECD Environmental Health and Safety Publication Series on Testing and Assessment No 67.
OECD Environmental Health and Safety Publication Series on Testing and Assessment No. 67.
OECD Guideline for the testing of chemicals No 425.
OECD Guideline for the testing of chemicals No 425.
Environmental Health and Safety Monograph Series on Testing and Assessment No 19.
OECD Environment, Health and Safety Publications Series on Testing and Assessment No. 19.
Environmental Health and Safety Monograph Series on Testing and Assessment No 24.
OECD Environment, Health and Safety Publications Series on Testing and Assessment No. 24.
B.55 HERSHBERGER BIOASSAY IN RATS:
B.55. HERSHBERGEROV BIOTEST NA ŠTAKORIMA:
A SHORT-TERM SCREENING ASSAY FOR (ANTI)ANDROGENIC PROPERTIES
KRATKOROČNI TEST PROBIRA ZA (ANTI)ANDROGENA SVOJSTVA
This test method is equivalent to OECD Test Guideline (TG) 441 (2009).
Ova ispitna metoda ekvivalentna je Smjernici za ispitivanje OECD-a TG 441 (2009.).
One element of the activity was to develop a test guideline for the rat Hershberger Bioassay.
Jedan element aktivnosti bio je razviti smjernice ispitivanja za Hershbergerov biotest na štakorima.
After several decades of use by the pharmaceutical industry, this assay was first standardised by an official expert committee in 1962 as a screening tool for androgenic chemicals (2).
Nakon nekoliko desetljeća korištenja u farmaceutskoj industriji ovaj je test 1962. godine prvo standardizirao službeni odbor stručnjaka kao alat probira za androgene kemikalije (2).
In 2001-2007, the rat Hershberger Bioassay has undergone an extensive validation programme including the generation of a Background Review Document (23), compilation of a detailed methods paper (3), development of a dissection guide (21) and the conduct of extensive intra- and interlaboratory studies to show the reliability and reproducibility of the bioassay.
U razdoblju 2001.–2007. Hershbergerov biotest na štakorima bio je podvrgnut opsežnom programu validacije koji je uključivao izradu Osnovnog dokumenta za preispitivanje (Background Review Document) (23), sastavljanje detaljnog dokumenta o metodama (3), izradu smjernica za disekcije (21) i provođenje opsežnih intralaboratorijskih i interlaboratorijskih studija radi dokazivanja pouzdanosti i obnovljivosti biotesta.
These validation studies were conducted with a potent reference androgen (testosterone propionate (TP)), two potent synthetic androgens (trenbolone acetate and methyl testosterone), a potent antiandrogenic pharmaceutical (flutamide), a potent inhibitor of the synthesis (finasteride) of the natural androgen (dihydrotestosterone-DHT), several weakly antiandrogenic pesticides (linuron, vinclozolin, procymidone, p,p' DDE), a potent 5α reductase inhibitor (finasteride) and two known negative chemicals (dinitrophenol and nonylphenol) (4) (5) (6) (7) (8).
Te validacijske studije provedene su upotrebom snažnog referentnog androgena (testosteron propionata (TP)), dvaju snažnih sintetskih androgena (trenbolon acetata i metil testosterona), snažnog antiandrogenog lijeka (flutamida), snažnog inhibitora sinteze (finasterida) prirodnog androgena (dihidrotestosterona – DHT), nekoliko slabo antiandrogenih pesticida (linurona, vinklozolina, procimidona, p,p' DDE), snažnog inhibitora 5α-reduktaze (finasterida) i dviju poznatih negativnih kemikalija (dinitrofenola i nonilfenola) (4) (5) (6) (7) (8).
This test method is the outcome of the long historical experience with the bioassay and the experience gained during the validation test programme and the results obtained therein.
Ova ispitna metoda rezultat je dugog povijesnog iskustva s biotestom i iskustva stečenog tijekom programa validacije ispitivanja i njime dobivenih rezultata.
The Hershberger Bioassay is a short-term in vivo screening test using accessory tissues of the male reproductive tract.
Hershbergerov biotest kratki je in vivo test probira u kojem se koriste pomoćna tkiva muškog reproduktivnog trakta.
The assay originated in the 1930s and was modified in the 1940s to include androgen-responsive muscles in the male reproductive tract (2) (9-15).
Test je uveden 1930-ih godina i izmijenjen 1940-ih godina tako da uključuje mišiće koji reagiraju na androgene u muškom reproduktivnom traktu (2) (9 – 15).
In the 1960s, over 700 possible androgens were evaluated using a standardised version of the protocol (2) (14), and use of the assay for both androgens and antiandrogens was considered a standard method in the 1960s (2) (15).
h godina ocjenjivano je preko 700 mogućih androgena upotrebom standardizirane verzije protokola (2) (14) te je 1960-ih godina upotreba testa i za androgene i za antiandrogene smatrana standardnom metodom (2) (15).
The current bioassay is based on the changes in weight of five androgen-dependent tissues in the castrate-peripubertal male rat.
Sadašnji biotest temelji se na promjenama mase pet tkiva ovisnih o androgenima kod kastriranih peripubertalnih mužjaka štakora.
It evaluates the ability of a chemical to elicit biological activities consistent with androgen agonists, antagonists or 5α-reductase inhibitors.
Njime se ocjenjuje sposobnost kemikalije da izazove biološko djelovanje koje odgovara agonistima androgena, antagonistima androgena ili inhibitorima 5α-reduktaze.
The five target androgen-dependent tissues included in this test method are the ventral prostate (VP), seminal vesicle (SV) (plus fluids and coagulating glands), levator ani-bulbocavernosus (LABC) muscle, paired Cowper's glands (COW) and the glans penis (GP).
Pet ciljnih tkiva ovisnih o androgenima obuhvaćenih ovom ispitnom metodom jesu: ventralna prostata (VP), sjemeni vezikul (SV) (uključujući tekućinu i koagulirajuće žlijezde), levator ani-bulbokavernozni mišić (LABC), parne Cowperove žlijezde (COW) i glans penisa (GP).
In the castrate-peripubertal male rat, these five tissues all respond to androgens with an increase in absolute weight.
U kastriranog peripubertalnog mužjaka štakora svih tih pet tkiva reagira na androgene povećanjem apsolutne mase.
When these same tissues are stimulated to increase in weight by administration of a potent reference androgen, these five tissues all respond to antiandrogens with a decrease in absolute weight.
Kada se ta tkiva stimuliraju na povećanje mase primjenom snažnog referentnog androgena, svih tih pet tkiva odgovara na antiandrogene smanjenjem apsolutne mase.
The primary model for the Hershberger bioassay has been the surgically castrated peripubertal male, which was validated in Phases 1, 2 and 3 of the Hershberger validation programme.
Primarni model za Hershbergerov biotest kirurški je kastrirani peripubertalni mužjak, koji je validiran u fazama 1., 2. i 3. programa validacije Hershbergerova biotesta.
The Hershberger bioassay serves as a mechanistic in vivo screening assay for androgen agonists, androgen antagonists and 5a-reductase inhibitors and its application should be seen in the context of the “OECD Conceptual Framework for the Testing and Assessment of Endocrine Disrupting Chemicals” (Appendix 2).
Hershbergerov biotest upotrebljava se kao mehanistički in vivo test probira za agoniste androgena, antagoniste androgena i inhibitore 5α-reduktaze te njegovu primjenu treba gledati u kontekstu ‚Konceptualnog okvira OECD-a za ispitivanje i ocjenjivanje kemikalija endokrinih disruptora’ (Dodatak 2.).
In this Conceptual Framework the Hershberger Bioassay is contained in Level 3 as an in vivo assay providing data about a single endocrine mechanism, i.e. (anti)androgenicity.
U tom Konceptualnom okviru Hershbergerov biotest sadržan je u razini 3. kao in vivo test kojim se dobivaju podaci o jednom endokrinom mehanizmu, tj. (anti)androgenosti.
It is intended to be included in a battery of in vitro and in vivo tests to identify chemicals with potential to interact with the endocrine system, ultimately leading to hazard and risk assessments for human health or the environment.
Namijenjen je da bude uključen u bateriju in vitro i in vivo testova za utvrđivanje kemikalija s potencijalom interakcije s endokrinim sustavom, što u konačnici dovodi do ocjene opasnosti i rizika za zdravlje ljudi ili za okoliš.
Due to animal welfare concerns with the castration procedure, the intact (uncastrated) stimulated weanling male was sought as an alternative model for the Hershberger Bioassay to avoid the castration step.
Radi zabrinutosti za dobrobit životinja zbog postupka kastracije, pokušalo se upotrijebiti intaktne (nekastrirane) stimulirane mužjake upravo odbijene od sise kao alternativnog modela za Hershbergerov biotest kako bi se izbjegla kastracija.
The stimulated weanling test method was validated (24);
Ispitna metoda sa stimuliranim mužjacima upravo odbijenima od sise validirana je (24);
however, in the validation studies, the weanling version of the Hershberger Bioassay did not appear to be able to consistently detect effects on androgen-dependent organ weights from weak anti-androgens at the doses tested.
međutim, tijekom validacijskih studija pokazalo se da verzijom Hershbergerova biotesta uz upotrebu mužjaka upravo odbijenih od sise nije moguće konzistentno utvrditi učinke na masu organa ovisnih o androgenima uz upotrebu slabih antiandrogena kod ispitivanih doza.
Therefore, it was not included in this test method.
Stoga ona nije uključena u ovu ispitnu metodu.
However, recognising that its use may provide not only animal welfare benefits but also may provide information on other modes of action, it is available in OECD Guidance Document 115(25).
Međutim, prepoznavajući da njezino korištenje ne pruža samo korist za dobrobit životinja, već da može pružiti i informacije o drugim načinima djelovanja, dostupna je u Smjernici OECD-a 115 (25).
Androgen agonists and antagonists act as ligands for the androgen receptor and may activate or inhibit, respectively, gene transcription controlled by the receptor.
Agonisti i antagonisti androgena djeluju kao ligandi za androgene receptore i mogu aktivirati odnosno inhibirati transkripciju gena koji kontrolira taj receptor.
In addition, some chemicals inhibit the conversion of testosterone to the more potent natural androgen dihydrotestosterone in some androgen target tissues (5a-reductase inhibitors).
Osim toga, neke kemikalije inhibiraju konverziju testosterona u snažniji prirodni androgen dihidrotestosteron u nekim ciljnim tkivima za androgene (inhibitori 5α-reduktaze).
Such chemicals have the potential to lead to adverse health hazards, including reproductive and developmental effects.
Takve kemikalije imaju potencijal uzrokovati štetne učinke po zdravlje, uključujući reproduktivne i razvojne učinke.
Therefore, the regulatory need exists to rapidly assess and evaluate a chemical as a possible androgen agonist or antagonist or 5a-reductase inhibitor.
Stoga postoji regulatorna potreba za brzom ocjenom i vrednovanjem kemikalije kao mogućeg agonista ili antagonista androgena ili inhibitora 5α-reduktaze.
While informative, the affinity of a ligand for an androgen receptor as measured by receptor binding or transcriptional activation of reporter genes in vitro is not the only determinant of possible hazard.
Iako informativan, afinitet liganda za androgeni receptor izmjeren vezanjem na receptor ili transkripcijskom aktivacijom gena izvjestitelja in vitro nije jedina determinanta moguće opasnosti.
Other determinants include metabolic activation and deactivation upon entering the body, chemical distribution to target tissues, and clearance from the body.
Druge determinante uključuju metaboličku aktivaciju i deaktivaciju nakon ulaska u tijelo, distribuciju kemikalije u ciljna tkiva i izlučivanje iz tijela.
This leads to the need to screen the possible activity of a chemical in vivo under relevant conditions and exposure.
Zbog toga se pojavljuje potreba probira na moguće djelovanje kemikalije in vivo pod odgovarajućim uvjetima i izloženosti.
In vivo evaluation is less critical if the chemical's characteristics regarding Absorption — Distribution — Metabolism — Elimination (ADME) are known.
In vivo vrednovanje manje je kritično ako su poznata svojstva kemikalije u pogledu Apsorpcije – Distribucije – Metabolizma – Uklanjanja (ADME).
Androgen-dependent tissues respond with rapid and vigorous growth to stimulation by androgens, particularly in castrate-peripubertal male rats.
Tkiva ovisna o androgenima odgovaraju brzim i snažnim rastom na stimulaciju androgenima, posebno u kastriranih peripubertalnih mužjaka štakora.
Therefore, the assay version, using the castrated peripubertal rat and the five target tissues in this assay, is appropriate for the in vivo screening of androgen agonists and antagonists and 5a-reductase inhibitors.
Stoga je verzija testa u kojoj se upotrebljavaju kastrirani peripubertalni štakori primjerena za in vivo probir agonista i antagonista androgena i inhibitora 5α-reduktaze.
This test method is based on those protocols employed in the OECD validation study which have been shown to be reliable and reproducible in intra- and inter-laboratory studies (4)(5)(6)(7)(8).
Ova ispitna metoda temelji se na protokolima korištenima u validacijskoj studiji OECD-a koja se pokazala pouzdanom i ponovljivom u intralaboratorijskim i interlaboratorijskim studijama (4) (5) (6) (7) (8).
Both androgen and antiandrogen procedures are presented in this test method.
U ovoj ispitnoj metodi prikazani su postupci i s androgenima i s antiandrogenima.
Although there was some variation in the dose of TP used to detect antiandrogens in the OECD Hershberger Bioassay validation programme by the different laboratories (0,2 versus 0,4 mg/kg/d, subcutaneous injection) there was little difference between these two protocol variations in the ability to detect weak or strong antiandrogenic activity.
Iako je bilo određenih varijacija u dozi TP-a upotrijebljenoj za utvrđivanje antiandrogena u programu validacije Hershbergerova biotesta OECD-a u različitim laboratorijima (0,2 u odnosu na 0,4 mg/kg/dnevno, supkutanom injekcijom), postojala je mala razlika između tih dviju varijanata protokola u pogledu sposobnosti utvrđivanja slabog ili snažnog antiandrogenog djelovanja.
However, it is clear that the dose of TP should not be too high to block the effects of weak androgen receptor (AR) antagonists or so low that the androgenic tissues display little growth response even without antiandrogen coadministration.
Međutim, jasno je da doza TP-a ne smije biti ni previsoka kako ne bi blokirala učinke slabih antagonista androgenih receptora (AR) ni tako niska da androgena tkiva pokažu slabu reakciju rasta čak i bez istovremene primjene antiandrogena.
The growth response of the individual androgen-dependent tissues is not entirely of androgenic origin, i.e. chemicals other than androgen agonists can alter the weight of certain tissues.
Reakcija rasta pojedinih tkiva ovisnih o androgenima nije u potpunosti androgenog podrijetla, tj. i druge kemikalije koje nisu agonisti androgena mogu uzrokovati promjenu mase određenih tkiva.
However, the growth response of several tissues concomitantly substantiates a more androgen-specific mechanism.
Međutim, reakcija istovremenog rasta nekoliko vrsta tkiva potkrepljuje postojanje mehanizma specifičnijeg za androgene.
For example, high doses of potent oestrogens can increase the weight of the seminal vesicles;
Na primjer, velike doze snažnih estrogena mogu povećati masu sjemenih vezikula;
however, the other androgen-dependent tissues in the assay do not respond in a similar manner.
međutim, druga tkiva ovisna o androgenima u testu ne reagiraju na sličan način.
Antiandrogenic chemicals can act either as androgen receptor antagonists or 5a-reductase inhibitors.
Antiandrogene kemikalije mogu djelovati ili kao antagonisti androgenih receptora ili kao inhibitori 5α-reduktaze.
reductase inhibitors have a variable effect, because the conversion to more potent dihydrotestosterone varies by tissue.
Inhibitori 5α-reduktaze imaju promjenjiv učinak zbog toga što se konverzija u snažniji dihidrotestosteron razlikuje s obzirom na vrstu tkiva.
Antiandrogens that inhibit 5α-reductase, like finasteride, have more pronounced effects in the ventral prostate than other tissues as compared to a potent AR antagonist, like flutamide.
Antiandrogeni koji inhibiraju 5α-reduktazu, kao što je finasterid, imaju izraženiji učinak na ventralnu prostatu nego na druga tkiva u usporedbi sa snažnim antagonistom AR-a, kao što je flutamid.
This difference in tissue response can be used to differentiate between AR mediated and 5α-reductase mediated modes of action.
Ova razlika u reakciji tkiva može se upotrebljavati za razlikovanje između načina djelovanja posredovanih AR-om i 5α-reduktazom.
In addition, the androgen receptor is evolutionarily related to that of other steroid hormones, and some other hormones, when administered at high, supraphysiological dosage levels, can bind and antagonise the growth-promoting effects of TP (13).
Osim toga, androgeni receptor evolucijski je povezan s receptorom drugih steroidnih hormona te neki drugi hormoni, kada se primijene u visokim, suprafiziološkim dozama, mogu vezati i antagonizirati učinke poticanja rasta TP-a (13).
Further, it also is plausible that enhanced steroid metabolism and a consequent lowering of serum testosterone could reduce androgen-dependent tissue growth.
Nadalje, vjerojatno je i da bi povećani metabolizam steroida i posljedično smanjenje testosterona u serumu mogli smanjiti rast tkiva ovisan o androgenima.
Therefore, any positive outcome in the Hershberger Bioassay should normally be evaluated using a weight of evidence approach, including in vitro assays, such as the AR and oestrogen receptor (ER) binding assays and corresponding transcriptional activation assays, or from other in vivo assays that examine similar androgen target tissues such as the male pubertal assay, 15-day intact adult male assay, or 28-day or 90-day repeat dose studies.
Stoga svaki pozitivan rezultat u Hershbergerovu biotestu treba uobičajeno vrednovati primjenom pristupa mase dokaza, uključujući testove in vitro, kao što su testovi vezivanja AR-a i estrogenskih receptora (ER) i odgovarajući testovi transkripcijske aktivacije, ili iz drugih testova in vivo kojima se ispituju slična ciljna tkiva za androgene kao što je test na pubertalnim mužjacima, 15-dnevni test na intaktnim odraslim mužjacima ili 28-dnevne ili 90-dnevne studije s ponovljenim dozama.
Experience indicates that xenobiotic androgens are rarer than xenobiotic antiandrogens.
Iskustvo upućuje na to da su ksenobiotski androgeni rjeđi od ksenobiotskih antiandrogena.
The expectation then is that the Hershberger bioassay will be used most often for the screening of antiandrogens.
Stoga je za očekivati da će se Hershbergerov biotest najčešće upotrebljavati za probir antiandrogena.
However, the procedure to test for androgens could, nevertheless, be recommended for steroidal or steroid-like chemicals or for chemicals for which an indication of possible androgenic effects was derived from methods contained in Level 1 or 2 of the conceptual framework (Appendix 2).
Međutim, bez obzira na to, postupak ispitivanja na androgene mogao bi se preporučiti za steroidne kemikalije ili kemikalije slične steroidima ili za kemikalije za koje pretpostavka mogućih androgenih učinaka proizlazi iz metoda sadržanih u razini 1. ili 2. konceptualnog okvira (Dodatak 2.).
Similarly, adverse effects associated with (anti)androgenic profiles may be observed in Level 5 assays, leading to the need to assess whether a chemical operates by an endocrine mode of action.
Slično tome, štetni učinci povezani s (anti)androgenim profilima mogu se uočiti u testovima razine 5., što dovodi do potrebe za procjenom djeluje li kemikalija endokrinim načinom djelovanja.
It is acknowledged that all animal-based procedures should conform to local standards of animal care;
Potvrđeno je da svi postupci u kojima se upotrebljavaju životinje trebaju biti sukladni s lokalnim standardima brige o životinjama;
the descriptions of care and treatment set forth below are minimal performance standards, and will be superseded by local regulations such as Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes (26).
opisi brige i tretmana navedeni u nastavku minimalni su standardi provedbe i bit će zamijenjeni lokalnim propisima kao što je Direktiva 2010/63/EU Europskog parlamenta i Vijeća od 22. rujna 2010. o zaštiti životinja koje se koriste u znanstvene svrhe (26).
Further guidance of the humane treatment of animals is given by the OECD (17).
OECD je dao dodatne smjernice o humanom postupanju sa životinjama (17).
As in any bioassay using experimental animals, careful considerations should be given to the necessity to carry out this study.
Kao i kod svih biotestova u kojima se koriste pokusne životinje, treba pomno razmotriti potrebu za provođenjem ove studije.
Basically there may be two reasons for such a decision:
U osnovi mogu postojati dva razloga za takvu odluku:
high exposure potential (Level 1 of the Conceptual Framework) or indications for (anti)androgenicity in in vitro assays (Level 2) supporting investigations whether such effects may occur in vivo;
velik potencijal izloženosti (razina 1. konceptualnog okvira) ili indikacije (anti)androgenosti u testovima in vitro (razina 2.) koji podupiru provedbu istraživanja o tome mogu li se takvi učinci pojaviti in vivo,
effects consistent with (anti)androgenicity in Level 4 or 5 in vivo tests supporting investigations of the specific mode of action, e.g. to determine whether the effects were due to an (anti)androgenic mechanism.
učinci koji upućuju na (anti)androgenost u in vivo testovima razine 4. ili 5. koji podupiru provedbu istraživanja specifičnog načina djelovanja, tj. kako bi se utvrdilo jesu li učinci posljedica (anti)androgenog mehanizma.
The Hershberger Bioassay achieves its sensitivity by using males with minimal endogenous androgen production.
Pri Hershbergerovu biotestu osjetljivost se postiže upotrebom mužjaka s minimalnom proizvodnjom androgena.
This is achieved through the use ofcastrated males provided an adequate time after castration for the target tissues to regress to a minimal and uniform baseline weight is allowed.
To se postiže upotrebom kastriranih mužjaka pod uvjetom da je nakon kastracije proteklo dovoljno vremensko razdoblje za regresiju ciljnih tkiva na minimalnu i ujednačenu polaznu masu.
Thus, when screening of potential androgenic activity, there are low endogenous levels of circulating androgens, the hypothalamic — pituitary — gonad axis is rendered unable to compensate via feedback mechanisms, the ability of the tissues to respond is maximised, and the starting tissue weight variability is minimised.
Tako kod probira potencijalnog androgenog djelovanja postoje niske endogene razine cirkulirajućih androgena, os hipotalamus – hipofiza – gonade nije to u stanju kompenzirati povratnim mehanizmima, sposobnost tkiva na reakciju je maksimizirana te je početna varijabilnost mase tkiva svedena na najmanju moguću mjeru.