natgillin/translations-raw huggingface dataset:
haematological tests;
hematološke pretrage,
clinical biochemistry tests;
kliničko-biokemijske pretrage,
urinalysis tests;
analiza urina,
outcome of any investigations of neurotoxicity or immunotoxicity;
ishod svih istraživanja neurotoksičnosti ili imunotoksičnosti,
terminal body weight;
tjelesna masa na kraju,
organ weights (and their ratios, if applicable);
mase organa (i njihovi omjeri ako je primjenjivo),
a detailed description of all treatment-related histopathological findings;
detaljan opis svih histopatoloških nalaza povezanih s tretiranjem,
Statistical treatment of results, as appropriate
Statistička obrada rezultata po potrebi
Discussion of results including:
Rasprava o rezultatima uključujući:
Dose: response relationships
Odnose doza i reakcija,
Consideration of any mode of action information
Razmatranja o svim načinima djelovanja informacija
Discussion of any modelling approaches
Rasprava o svim modelima pristupa
BMD, NOAEL or LOAEL determination
Određivanje BMD, NOAEL ili LOAEL
Historical control data
Povijesni kontrolni podaci
Relevance for humans
Relevantnost za ljude
Chapter B.27 of this Annex, Sub-chronic Oral Toxicity Test Repeated Dose 90-day Oral Toxicity Study in Non-Rodents.
Poglavlje B.27 ovog Priloga, Test subkronične oralne toksičnosti - 90-dnevna studija oralne toksičnosti na neglodavcima uz primjenu ponavljanih doza.
Guidance Document on the Design and Conduct of Chronic Toxicity and Carcinogenicity Studies, Supporting Test Guidelines 451, 452 and 453 — Second edition.
Guidance Document on the Design and Conduct of Chronic Toxicity and Carcinogenicity Studies, Supporting Test Guidelines 451, 452 and 453 - Second edition. Series on Testing and Assessment No.
Guidance Document on Acute Inhalation Toxicity Testing, Series on Testing and Assessment No 39, ENV/JM/MONO(2009)28, OECD, Paris.
39, ENV/JM/MONO(2009)28, OECD, Pariz.
Chapter B.8 of this Annex, Subacute Inhalation Toxicity: 28-Day Study.
Poglavlje B.8 ovog Priloga, Subakutna inhalacijska toksičnost: 28-dnevna studija.
Chapter B.29 of this Annex, Subchronic Inhalation Toxicity: 90-Day Study.
Poglavlje B.29 ovog Priloga, Subkronična inhalacijska toksičnost: 90-dnevna studija.
Chapter B.9 of this Annex, Repeated Dose (28 Days) Toxicity (Dermal).
Poglavlje B.9 ovog Priloga, Toksičnost (dermalna) pri ponavljanoj dozi (28 dana).
Guidance Notes for Analysis and Evaluation of Chronic Toxicity and Carcinogenicity Studies, Series on Testing and Assessment No 35 and Series on Pesticides No 14, ENV/JM/MONO(2002)19, OECD, Paris.
35 and Series on Pesticides No. 14, ENV/JM/MONO(2002)19, OECD, Pariz.
Guidance Document on the recognition, assessment, and use of clinical signs as humane endpoints for experimental animals used in safety evaluation, No 19, ENV/JM/MONO(2000)7, OECD, Paris.
19, ENV/JM/MONO(2000)7, OECD, Pariz.
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 (OJ L 276, 20.10.2010, p. 33).
Direktiva 2010/63/EU Europskog parlamenta i Vijeća od 22. rujna 2010. o zaštiti životinja koje se upotrebljavaju u znanstvene svrhe, SL L 276, 20.10.2010., str. 33.
EMEA (draft) document “Non-clinical guideline on drug-induced hepatotoxicity” (Doc. Ref. EMEA/CHMP/SWP/a50115/2006).
EMEA (draft) document ‚Non-clinical guideline on drug-induced hepatotoxicity’ (Doc. Ref. EMEA/CHMP/SWP/a50115/2006).
Chapters B.32 and B.33 are replaced by the following:
Poglavlja B.32 i B.33 mijenjaju se i glase:
CARCINOGENICITY STUDIES
STUDIJE KARCINOGENOSTI
This Test Method is equivalent to OECD Test Guideline (TG) 451 (2009).
Ova je ispitna metoda ekvivalentna Smjernici za ispitivanje OECD-a (TG) 451 (2009.).
The updating of this Test Method B.32 has been carried out in parallel with revisions of Chapter B.30 of this Annex, Chronic Toxicity Studies, and Chapter B.33, of this Annex, Combined Chronic ToxicityCarcinogenicity Studies, and with the objective of obtaining additional information from the animals used in the study and providing further detail on dose selection.
Ova ispitna metoda B.32 ažurirana je paralelno s revizijama Poglavlja B.30 ovog Priloga, Studije kronične toksičnosti te Poglavlja B.33 ovog Priloga, Kombinirane studije kronične toksičnosti/karcinogenosti te s ciljem pribavljanja dodatnih informacija od životinja korištenih u studiji te prikupljanja daljnjih pojedinosti o odabiru doze.
This Test Method B.32 is designed to be used in the testing of a broad range of chemicals, including pesticides and industrial chemicals.
Ova ispitna metoda B.32 namijenjena je primjeni u ispitivanju širokog spektra kemikalija, uključujući pesticide i industrijske kemikalije.
It should be noted however that some details and requirements may differ for pharmaceuticals (see International Conference on Harmonisation (ICH) Guidance S1B on Testing for Carcinogenicity of Pharmaceuticals).
No, treba imati na umu da neke pojedinosti i zahtjevi mogu biti različiti za ljude (vidjeti Smjernicu S1B o Ispitivanju kancerogenosti lijekova Međunarodne konferencije o usklađivanju (International conference on Harmonisation (ICH)).
The majority of carcinogenicity studies are carried out in rodent species, and this Test Method is intended therefore to apply primarily to studies carried out in these species.
Većina studija karcinogenosti provodi se na vrstama glodavaca, stoga i ovu ispitnu metodu treba primjenjivati prvenstveno u studijama koje se provode na tim vrstama.
Should such studies be required in non-rodent species, the principles and procedures outlined in this Test Method together with those outlined in Chapter B.27 of this Annex, Repeated Dose 90-day Oral Toxicity Study in Non-Rodents (6), should be applied, with appropriate modifications.
Ako se traži da se studije provode na neglodavcima, treba primijeniti načela i postupke izložene u ovoj ispitnoj metodi uz odgovarajuće modifikacije zajedno s načelima i postupcima izloženima u Poglavlju B.27 ovog Priloga, Studija subkronične oralne toksičnosti-90-dnevna studija oralne toksičnosti na neglodavcima uz primjenu ponavljanih doza (6)-.
Further guidance is available in the OECD Guidance Document No 116 on the Design and Conduct of Chronic Toxicity and Carcinogenicity Studies (7).
Ostale upute dostupne su u Smjernici br. 116. o planiranju i provođenju studija kronične toksičnosti i kancerogenosti (7).
The three main routes of administration used in carcinogenicity studies are oral, dermal and inhalation.
Tri glavna načina primjene korištena u studijama kancerogenosti jesu oralni, dermalni i inhalacijski.
Additional information on choice of route of exposure is provided in Guidance Document No 116 (7).
Dodatne informacije o odabiru načina izlaganja navedene su u Smjernici br. 116. (7).
This Test Method focuses on exposure via the oral route, the route most commonly used in carcinogenicity studies.
Ova ispitna metoda usmjerena je na izlaganje oralnim putem, što je najčešće korišteni način u studijama karcinogenosti.
While carcinogenicity studies involving exposure via the dermal or inhalation routes may also be necessary for human health risk assessment and/or may be required under certain regulatory regimes, both routes of exposure involve considerable technical complexity.
Dok dugotrajne studije karcinogenosti, koje uključuju izlaganje preko kože ili inhalacijom, mogu također biti potrebne i/ili se mogu tražiti pod određenim regulatornim režimima radi određivanja rizika za ljude, oba načina izlaganja uključuju znatnu tehničku složenost.
Such studies will need to be designed on a case-by-case basis, although the Test Method outlined here for the assessment and evaluation of carcinogenicity by oral administration could form the basis of a protocol for inhalation and/or dermal studies, with respect to recommendations for treatment periods, clinical and pathology parameters, etc. OECD Guidance is available on the administration of test chemicals by the dermal (7), and inhalation routes (7) (8).
Takve studije treba planirati za svaki slučaj posebno iako ovdje izložena ispitna metoda za određivanje i ocjenu karcinogenosti putem oralne primjene može poslužiti kao temelj za protokol za studije inhalacijom i/ili dermalnim putem, uzimajući u obzir razdoblja tretiranja, kliničke i patološke parametre itd. Dostupna je OECD-ova Smjernica za primjenu ispitivane kemikalije dermalnim (7) i inhalacijskim putem (7) (8).
Chapter B.8 of this Annex (9) and Chapter B.29 of this Annex (10), together with the OECD Guidance Document on acute inhalation testing (8), should be specifically consulted in the design of longer term studies involving exposure via the inhalation route.
Poglavlje B.8 ovog Priloga (9) i Poglavlje B.29 ovog Priloga (10), zajedno sa Smjernicom OECD-a za ispitivanje akutne inhalacije (8), trebaju poslužiti kao detaljna konzultacija pri planiranju dugotrajnijih studija koje uključuju izlaganje inhalacijom.
Chapter B.9 of this Annex (11) should be consulted in the case of testing carried out by the dermal route.
Poglavlje B.9 ovog Priloga (11) treba uzeti kao pomoć pri ispitivanju provedenom dermalnim putem.
The carcinogenicity study provides information on the possible health hazards likely to arise from repeated exposure for a period lasting up to the entire lifespan of the species used.
Studija karcinogenosti pruža informacije o mogućim rizicima za zdravlje koji će se vjerojatno pojaviti zbog ponovljenog izlaganja kroz gotovo čitavo ili čitavo životno razdoblje korištenih vrsta.
The study will provide information on the toxic effects of the test chemical including potential carcinogenicity, and may indicate target organs and the possibility of accumulation.
Ta će studija pružiti informacije o toksičnim učincima ispitivane kemikalije, uključujući i potencijalnu karcinogenost te može ukazati na organe mete i mogućnost akumulacije.
It can provide an estimate of the no-observed-adverse effect level for toxic effects and, in the case of non-genotoxic carcinogens, for tumour responses, which can be used for establishing safety criteria for human exposure.
Može pružiti procjenu razine neopaženih štetnih učinaka te, u slučaju negenotoksičnih karcinogena, za tumorske reakcije koje se mogu upotrijebiti za određivanje sigurnosnih kriterija za izlaganje ljudi.
The objectives of carcinogenicity studies covered by this Test Method include:
Ciljevi studija karcinogenosti obuhvaćenih ovom ispitnom metodom uključuju:
The identification of the carcinogenic properties of a test chemical, resulting in an increased incidence of neoplasms, increased proportion of malignant neoplasms or a reduction in the time to appearance of neoplasms, compared with concurrent control groups;
Identifikaciju karcinogenih svojstava ispitivane kemikalije koja rezultiraju povećanjem učestalosti pojavljivanja neoplazmi, povećanim omjerom malignih neoplazmi ili smanjenjem u vrijeme pojavljivanja neoplazmi u usporedbi s paralelnim kontrolnim skupinama,
The identification of target organ(s) of carcinogenicity;
Identifikaciju organa meta karcinogenosti,
The identification of the time to appearance of neoplasms;
Identifikaciju vremena pojavljivanja neoplazmi,
Characterisation of the tumour dose-response relationship;
Karakterizaciju odnosa doze i reakcije za tumor,
Extrapolation of carcinogenic effects to low dose human exposure levels;
Ekstrapolaciju karcinogenih učinaka na niskim razinama izlaganja ljudi,
Provision of data to test hypotheses regarding mode of action (2) (7) (12) (13) (14) (15).
Pružanje podataka za ispitivanje pretpostavki u svezi s načinom djelovanja (2) (7) (12) (13) (14) (15).
In the assessment and evaluation of the potential carcinogenicity of a test chemical, all available information on the test chemical should be considered by the testing laboratory prior to conducting the study, in order to focus the design of the study to more efficiently test for carcinogenic potential and to minimise animal usage.
U određivanju i procjeni potencijalne karcinogenosti ispitivane kemikalije laboratorij koji provodi ispitivanje prije provođenja studije mora u obzir uzeti sve dostupne informacije o ispitivanoj kemikaliji kako bi se plan studije usmjerio na učinkovitije ispitivanje potencijala karcinogenosti te kako bi se na minimum svela primjena životinja.
Information on, and consideration of, the mode of action of a suspected carcinogen (2) (7) (12) (13) (14) (15) is particularly important, since the optimal design may differ depending on whether the test chemical is a known or suspected genotoxic carcinogen.
Informacije i razmatranja o svim načinima djelovanja karcinogena na koji se sumnja (2) (7) (12) (13) (14) (15) posebno su važne jer se optimalan plan može razlikovati, ovisno o tome zna li se ili sumnja za ispitivanu kemikaliju da je genotoksični karcinogen.
Further guidance on mode of action considerations can be found in Guidance Document No 116 (7).
Ostale upute o razmatranju načina djelovanja mogu se pronaći u Smjernici br. 116. (7).
Information that will assist in the study design includes the identity, chemical structure, and physico-chemical properties of the test chemical; results of any in vitro or in vivo toxicity tests including genotoxicity tests; anticipated use(s) and potential for human exposure; available (Q)SAR data, mutagenicity/genotoxicity, carcinogenicity and other toxicological data on structurally-related chemicals; available toxicokinetic data (single dose and also repeat dose kinetics where available) and data derived from other repeated exposure studies.
Informacije koje će pomoći u planiranju istraživanja obuhvaćaju identitet, kemijsku strukturu i fizikalno-kemijska svojstva ispitivane kemikalije, rezultate svih ispitivanja toksičnosti in vitro ili in vivo uključujući ispitivanja genotoksičnosti; očekivanu/e primjenu/e i potencijal za ljudsko izlaganje, dostupne podatke (Q)SAR, mutagenost/genotoksičnost, karcinogenost i druge toksikološke podatke o kemikalijama srodne strukture, dostupne toksikokinetičke podatke (kinetika jedne doze i ponovljene doze ako je dostupno) te podatke dobivene drugim istraživanjima s ponovljenim izlaganjem.
Assessment of carcinogenicity should be carried out after initial information on toxicity has been obtained from repeated dose 28-day and/or 90-day toxicity tests.
Određivanje karcinogenosti treba provesti nakon dobivanja početnih informacija o toksičnosti iz 28-dnevnog i/ili 90-dnevnog ispitivanja toksičnosti uz primjenu ponavljanih doza.
Short-term cancer initiation-promotion tests could also provide useful information.
Kratkoročno ispitivanje početnog razvoja raka također može pružiti korisne informacije.
A phased testing approach to carcinogenicity testing should be considered as part of the overall assessment of the potential adverse health effects of a particular test chemical (16) (17) (18) (19).
Pristup s fazama u ispitivanju karcinogenosti treba smatrati dijelom ukupnog utvrđivanja potencijalno štetnih učinaka dotične ispitivane kemikalije po zdravlje (16) (17) (18) (19).
Issues to consider include whether the statistics should include adjustment for survival, analysis of cumulative tumour risks relative to survival duration, analysis of the time to tumour and analysis in the event of premature termination of one or more groups.
Problemi koja treba razmatrati uključuju treba li statistika uključivati prilagodbu preživjelih, analizu ukupnog rizika od tumora u odnosu na trajanje preživljavanja, analizu vremena za stvaranje tumora te analizu u slučaju prijevremenog svršetka jedne ili više skupina.
Guidance on the appropriate statistical analyses and key references to internationally accepted statistical methods are given in Guidance Document No 116 (7), and also in Guidance Document No 35 on the analysis and evaluation of chronic toxicity and carcinogenicity studies (20).
Smjernice o odgovarajućim statističkim analizama i ključnim referencama na međunarodno prihvaćene statističke metode nalaze se u Smjernici br. 116. (7) te također u Smjernici br. 35. za analizu i ocjenu studija kronične toksičnosti i karcinogenosti (20).
In conducting a carcinogenicity study, the guiding principles and considerations outlined in the OECD Guidance Document No 19 on the recognition, assessment, and use of clinical signs as humane endpoints for experimental animals used in safety evaluation (21), in particular paragraph 62 thereof, should always be followed.
Pri provođenju istraživanja karcinogenosti uvijek treba slijediti načela i razloge izložene u OECD-ovoj Smjernici br. 19. o prepoznavanju, određivanju i primjeni kliničkih znakova kao humanih krajnjih ishoda za pokusne životinje korištene u procjeni sigurnosti (21) posebno u stavku 62.
Detailed guidance on and discussion of the principles of dose selection for chronic toxicity and carcinogenicity studies can be found in Guidance Document No 116 (7) as well as two International Life Sciences Institute publications (22) (23).
Detaljne upute za načela odabira doza za studije kronične toksičnosti i karcinogenosti te rasprava o njima mogu se pronaći u Smjernici br. 116. (7), kao i u dvije publikacije instituta International Life Sciences Institute (22) (23).
This is particularly relevant in the situation where a combined chronic toxicity and carcinogenicity study (Chapter B.33 of this Annex) is to be carried out (paragraph 12).
To je posebno relevantno u situaciji u kojoj treba provesti kombiniranu studiju kronične toksičnosti i karcinogenosti (Poglavlje B.33 ovog Priloga) (stavak 12.).
Consideration should be given to carrying out a combined chronic toxicity and carcinogenicity study (Chapter B.33 of this Annex), rather than separate execution of a chronic toxicity study (Chapter B.30 of this Annex) and carcinogenicity study (this Test Method B.32).
Treba navesti razloge za provođenje kombinirane studije kronične toksičnosti i karcinogenosti (Poglavlje B.33 ovog Priloga), a ne odvojeno provođenje studije kronične toksičnosti (Poglavlje B.30 ovog Priloga) i studije karcinogenosti (ova ispitna metoda B.32).
Careful consideration should however be given to the principles of dose selection (paragraphs 11 and 22-25) when undertaking a combined chronic toxicity and carcinogenicity study (Chapter B.33 of this Annex), and it is also recognised that separate studies may be required under certain regulatory frameworks.
Pri provođenju kombinirane studije kronične toksičnosti i karcinogenosti (Poglavlje B.33 ovog Priloga) treba pažljivo razmisliti o načelima odabira doza (stavci 11. i 22. - 25.) te se također priznaje da pod određenim regulatornim okvirima mogu biti nužne odvojene studije.
Definitions used in the context of this Test Method can be found at the end of this chapter and in the Guidance Document No 116 (7).
Definicije upotrijebljene u kontekstu ove ispitne metode nalaze se na kraju ovog poglavlja i u Smjernici br. 116. (7).
The test chemical is administered daily in graduated doses to several groups of test animals for the majority of their life span, normally by the oral route.
Ispitivana kemikalija primjenjuje se svakodnevno u stupnjevanim dozama raznim skupinama pokusnih životinja tijekom najvećeg dijela njihova životnog vijeka, obično oralnim putem.
Testing by the inhalation or dermal route may also be appropriate.
Može biti prikladno i ispitivanje inhalacijom ili dermalnim putem.
The animals are observed closely for signs of toxicity and for the development of neoplastic lesions.
Životinje se pomno promatraju radi znakova toksičnosti i razvoja neoplazmičkih lezija.
DESCRIPTION OF METHOD
OPIS METODE
This Test Method primarily covers assessment and evaluation of carcinogenicity in rodents (paragraph 2).
Ova ispitna metoda prvenstveno obuhvaća određivanje i ocjenu karcinogenosti u glodavaca (stavak 2.).
The use of non-rodent species may be considered when available data suggest that they are more relevant for the prediction of health effects in humans.
U obzir se može uzeti primjena vrsta neglodavaca ako dostupni podaci sugeriraju da su oni relevantniji za predviđanje zdravstvenih učinaka po ljude.
The preferred rodent species is the rat, although other rodent species, e.g. the mouse, may be used.
Preferirana vrsta glodavaca jesu štakori iako se mogu upotrijebiti i druge vrste glodavaca, npr. miš.
Although the use of the mouse in carcinogenicity testing may have limited utility (24) (25) (26), under some current regulatory programmes carcinogenicity testing in the mouse is still required unless it is determined that such a study is not scientifically necessary.
Iako uporaba miševa u ispitivanju karcinogenosti može biti ograničeno korisna (24) (25) (26), u nekim aktualnim regulatornim programima još se uvijek traži ispitivanje karcinogenosti u miševa osim ako je utvrđeno da nema znanstvene potrebe za takvom studijom.
Additional information on choice of species and strain is provided in Guidance Document No 116 (7).
Dodatne informacije o odabiru vrste i soja navedene su u Smjernici br. 116. (7).
The carcinogenicity study should preferably be carried out in animals from the same strain and source as those used in preliminary toxicity study(ies) of shorter duration although, if animals from this strain and source are known to present problems in achieving the normally accepted criteria of survival for long-term studies [see Guidance Document No 116 (7)], consideration should be given to using a strain of animal that has an acceptable survival rate for the long-term study.
Studiju karcinogenosti treba po mogućnosti obaviti na životinjama istog soja i podrijetla kao i životinje korištene u preliminarnoj/im studiji/-ama toksičnosti kraćeg trajanja ako se za životinje tog soja i podrijetla zna da imaju problema u postizanju uobičajeno prihvaćenih kriterija za preživljavanje u dugotrajnim istraživanjima [vidjeti Smjernicu br. 116. (9)], treba razmotriti primjenu životinjskog soja s prihvatljivom stopom preživljavanja za dugotrajnu studiju.
Animals may be housed individually, or be caged in small groups of the same sex; individual housing should be considered only if scientifically justified (27) (28) (29).
Životinje moraju biti smještene pojedinačno ili u kavezima u malim skupinama istog spola; pojedinačni smještaj treba uzeti u obzir samo ako je znanstveno opravdan (27) (28) (29).
The temperature in the experimental animal room should be 22 °C (± 3 °C).
Temperatura u prostoriji s pokusnim životinjama trebala bi iznositi 22 °C (± 3 °C).
The diet should meet all the nutritional requirements of the species tested and the content of dietary contaminants, including but not limited to pesticide residues, persistent organic pollutants, phytoestrogens, heavy metals and mycotoxins, that might influence the outcome of the test, should be as low as possible.
Prehrana mora ispunjavati sve nutritivne potrebe ispitivanih vrsta, a udio tvari koje kontaminiraju hranu - uključujući ostatke pesticida, postojane organske zagađivače, fitoestrogene, teške metale i mikotoksine, ali ne ograničeno na njih - koje mogu utjecati na rezultat ispitivanja treba biti što je moguće manji.
At the commencement of the study, the weight variation for each sex of animal used should be minimal and not exceed ± 20 % of the mean weight of all the animals within the study, separately for each sex.
Na početku studije odstupanje u masi za svaki spol korištenih životinja mora biti minimalno i ne smije biti veće od ± 20 % prosječne mase svih životinja u studiji, posebno za svaki spol.
A sufficient number of animals should be used so that a thorough biological and statistical evaluation is possible.
Treba upotrijebiti dovoljan broj životinja tako da se omogući temeljita biološka i statistička ocjena.
Each dose group and concurrent control group should therefore contain at least 50 animals of each sex.
Stoga svaka skupina koja prima dozu i paralelna kontrolna skupina moraju sadržavati najmanje 50 životinja svakog spola.