natgillin/translations-raw huggingface dataset:
If a test at one dose level of at least 1000 mg/kg body weight/day by oral administration, using the procedures described for this study, produces no observable toxicity in either pregnant animals or their progeny and if an effect would not be expected based upon existing data (e.g. from structurally and/or metabolically related compounds), then a full study using three dose levels may not be considered necessary.
Če preskus pri eni velikosti odmerka najmanj 1000 mg/kg telesne mase/dan z oralnim dajanjem, pri katerem se uporabijo postopki, opisani za to študijo, ne povzroči opazne toksičnosti pri nobeni breji živali ali njenih potomcih in če se glede na obstoječe podatke (npr. o strukturno in/ali presnovno sorodnih zmeseh) ne pričakuje učinka, potem se šteje, da ni potrebna popolna študija z uporabo treh velikosti odmerkov.
Expected human exposure may indicate the need for a higher oral dose level to be used in the limit test.
Pričakovana človekova izpostavljenost lahko narekuje potrebo, da se v mejnem preskusu uporabi večji oralni odmerek.
For other types of administration, such as inhalation or dermal application, the physico-chemical properties of the test substance often may indicate and limit the maximum attainable level of exposure (for example, dermal application should not cause severe local toxicity).
Pri drugih vrstah dajanja, na primer pri vdihavanju ali dermalni aplikaciji, lahko fizikalno-kemijske lastnosti preskusne snovi pogosto določajo in omejujejo največjo dosegljivo raven izpostavljenosti (na primer dermalna aplikacija ne bi smela povzročati hude lokalne toksičnosti).
The test substance or vehicle is usually administered orally by intubation.
Preskusna snov ali nosilec se navadno daje oralno z intubacijo.
If another route of administration is used, the tester should provide justification and reasoning for its selection, and appropriate modifications may be necessary (2)(3)(4).
Če se uporabi drug način dajanja odmerkov, mora izvajalec preskusa zagotoviti utemeljitev in razlog za svojo izbiro, lahko pa so potrebne ustrezne spremembe (2)(3)(4).
The test substance should be administered at approximately the same time each day.
Preskusno snov je treba dati vsak dan približno ob istem času.
The dose to individual animals should normally be based on the most recent individual body weight determination.
Odmerek za posamezno žival navadno temelji na zadnji posamični določitvi telesne mase.
However, caution should be exercised when adjusting the dose during the last trimester of pregnancy.
Vendar je potrebna previdnost pri prilagajanju odmerka v zadnjem trimestni brej osti.
Existing data should be used for dose selection to prevent excess maternal toxicity.
Pri izbiri odmerka je treba uporabiti obstoječe podatke, da bi preprečili čezmerno toksičnost pri materi.
However, if excess toxicity is noted in the treated dams, those animals should be humanely killed.
Če se pri tretiranih materah opazi čezmerna toksičnost, je treba te živali humano usmrtiti.
If several pregnant animals show signs of excess toxicity, consideration should be given to terminating that dose group.
Če več živali kaže znake čezmerne toksičnosti, je treba razmisliti o prekinitvi te skupine odmerka.
When the substance is administered by gavage, this should preferably be given as a single dose to the animals using a stomach tube or a suitable intubation canula.
Če se snov daje z gavažo, jo je treba dati živali po možnosti v enkratnem odmerku z uporabo želodčne sonde ali primerne intubacijske kanile.
When corn oil is used as a vehicle, the volume should not exceed 0.4 ml/100 g body weight.
Če se kot nosilec uporablja koruzno olje, količina ne sme presegati 0,4 ml/100 g telesne mase.
Variability in test volume should be minimised by adjusting the concentrations to ensure a constant volume across all dose levels.
Variabilnost preskusne količine je treba s prilagajanjem koncentracije obdržati na kar najnižji ravni, da se zagotovi konstantna količina pri vseh odmerkih.
Observations of the dams
Opazovanje mater
Clinical observations should be made and recorded at least once a day, preferably at the same time(s) each day taking into consideration the peak period of anticipated effects after dosing.
Klinična opazovanja je treba opraviti in dokumentirati najmanj enkrat na dan, najbolje vsak dan ob istem času, pri čemer se upošteva vrhunec pričakovanih učinkov po odmerjanju.
The condition of the animals should be recorded including mortality, moribundity, pertinent behavioural changes, and all signs of overt toxicity.
Stanje živali je treba dokumentirati, vključno s smrtnostjo, odmiranjem, pomembnimi vedenjskimi spremembami in vsemi znaki očitne toksičnosti.
Body weight and food consumption
Telesna masa in poraba hrane
Animals should be weighed on day 0 of gestation or no later than day 3 of gestation if time-mated animals are supplied by an outside breeder, on the first day of dosing, at least every three days during the dosing period and on the day of scheduled kill.
Živali je treba stehtati na dan brejosti 0 ali najpozneje tretji dan brejosti, če je živali, ki so se parile, dostavil zunanji rejec, nato na prvi dan odmerjanja, najmanj vsake 3 dni v obdobju odmerjanja in na dan predvidene usmrtitve.
Food consumption should be recorded at three-day intervals and should coincide with days of body weight determination.
Porabo hrane je treba zabeležiti vsake tri dni, na isti dan kot se določa telesna masa.
Post-mortem examination
Postmortalni pregled
Females should be killed one day prior to the expected day of delivery.
Samice je treba usmrtiti en dan pred pričakovano kotitvijo.
Females showing signs of abortion or premature delivery prior to scheduled kill should be killed and subjected to a thorough macroscopic examination.
Samice, ki kažejo znake splava ali predčasne kotitve pred predvideno usmrtitvijo, je treba usmrtiti in opraviti temeljit makroskopski pregled.
At the time of termination or death during the study, the dam should be examined macroscopically for any structural abnormalities or pathological changes.
Ob koncu študije ali ob smrti med študijo se makroskopsko pregledajo kakršne koli strukturne anomalije ali patološke spremembe pri materi.
Evaluation of the dams during caesarean section and subsequent foetal analyses should be conducted preferably without knowledge of treatment group in order to minimise bias.
Ocenitev matere med carskim rezom in poznejše analize fetusa naj se izvajajo po možnosti brez poznavanja tretirane skupine, da je pristranskost čim manjša.
Examination of uterine contents
Pregled maternične vsebine
Immediately after termination or as soon as possible after death, the uteri should be removed and the pregnancy status of the animals ascertained.
Takoj po koncu študije ali čim prej po smrti se maternice odstranijo in ugotovi status nosečnosti živali.
Uteri that appear non gravid should be further examined (e.g. by ammonium sulphide staining for rodents and Salewski staining or a suitable alternative method for rabbits) to confirm the non-pregnant status (5).
Maternice, ki niso videti gravidne, se še dodatno pregledajo (npr. z barvanjem z amonijevim sulfidom pri glodalcih in barvanjem po Salewskem ali ustrezno alternativno metodo pri kuncih), da se potrdi nenoseči status (5).
Gravid uteri including the cervix should be weighed.
Gravidne maternice z materničnim vratom je treba stehtati.
Gravid uterine weights should not be obtained from animals found dead during the study.
Masa gravidnih maternic se ne sme pridobiti od živali, za katere je ugotovljeno, da so med študijo poginile.
The number of corpora lutea should be determined for pregnant animals.
Pri brejih živalih se določi število rumenih telesc.
The uterine contents should be examined for numbers of embryonic or foetal deaths and viable foetuses.
Maternično vsebino je treba pregledati glede na število embrionalnih ali fetalnih smrti in fetusov, ki so sposobni preživetja.
The degree of resorption should be described in order to estimate the relative time of death of the conceptus (see Section 1.2).
Opisati je treba stopnjo resorpcije, da bi ocenili relativni čas smrti zarodka (glej oddelek 1.2).
Examination of foetuses
Pregled fetusov
The sex and body weight of each foetus should be determined.
Za vsak fetus je treba določiti spol in telesno maso.
Each foetus should be examined for external alterations (6).
Pri vsakem fetusu je treba pregledati zunanje spremembe (6).
Foetuses should be examined for skeletal and soft tissue alterations (e.g. variations and malformations or anomalies) (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24).
Pregledajo se spremembe skeleta in mehkega tkiva pri fetusih (npr. odstopanja in deformnosti ali nepravilnosti) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) (20) (21) (22) (23) (24).
Categorisation of foetal alterations is preferable but not required.
Kategorizacija fetalnih sprememb je zaželena, vendar ne nujna.
When categorisation is done, the criteria for defining each category should be clearly stated.
Kadar se opravi kategorizacija, je treba jasno navesti merila za določitev vsake kategorije.
Particular attention should be paid to the reproductive tract which should be examined for signs of altered development.
Posebno pozornost je treba posvetiti reproduktivnemu traktu, ki ga je treba pregledati, če ima znake spremenjenega razvoja.
For rodents, approximately one-half of each litter should be prepared and examined for skeletal alterations.
Pri glodalcih je treba pripraviti približno polovico vsakega zaroda in pregledati skeletne spremembe.
The remainder should be prepared and examined for soft tissue alterations, using accepted or appropriate serial sectioning methods or careful gross dissection techniques.
Druga polovica se pripravi in pregleda glede sprememb mehkega tkiva s sprejetimi ali ustreznimi metodami serijskega razreza ali s tehnikami natančne osnovne raztelesbe.
For non-rodents, e.g. rabbits, all foetuses should be examined for both soft tissue and skeletal alterations.
Pri neglodalcih, npr. kuncih, se pri vseh fetusih pregledajo spremembe mehkega tkiva in skeleta.
The bodies of these foetuses are evaluated by careful dissection for soft tissue alterations, which may include procedures to further evaluate internal cardiac structure (25).
Pri telesih teh fetusov se spremembe mehkega tkiva ocenijo z natančno raztelesbo, ki lahko vključuje postopke za dodatno oceno notranje strukture srca (25).
The heads of one-half of the foetuses examined in this manner should be removed and processed for evaluation of soft tissue alterations (including eyes, brain, nasal passages and tongue), using standard serial sectioning methods (26) or an equally sensitive method.
Glave polovice fetusov, ki so pregledani na ta način, se odstranijo in obdelajo za oceno sprememb mehkega tkiva (tudi oči, možganov, nosnih prehodov in jezika) z uporabo standardnih metod serijskega razreza (26) ali enako občutljivih metod.
The bodies of these foetuses and the remaining intact foetuses should be processed and examined for skeletal alterations, utilising the same methods as described for rodents.
Telesa teh fetusov in preostalih nedotaknjenih fetusov se obdelajo in pregledajo glede skeletnih sprememb z enakimi metodami, kakor so opisane za glodalce.
Data shall be reported individually for the dams as well as for their offspring and summarised in tabular form, showing for each test group and each generation the number of animals at the start of the test, the number of animals found dead during the test or killed for humane reasons, the time of any death or humane kill, the number of pregnant females, the number of animals showing signs of toxicity, a description of the signs of toxicity observed, including time of onset, duration, and severity of any toxic effects, the types of embryo/foetal observations, and all relevant litter data.
Podatki se sporočajo posamično za matere in njihove potomce in se povzamejo v obliki tabele, ki prikazuje za vsako preskusno skupino in vsako generacijo število živali na začetku preskusa, število živali, najdenih mrtvih ali usmrčenih iz humanih razlogov med preskusom, čas katere koli smrti ali humane usmrtitve, število brejih samic, število živali, ki kažejo znake toksičnosti, opis znakov zaznane toksičnosti, vključno s časom začetka, trajanja in resnosti katerih koli toksičnih učinkov, vrsto embrionalnih/fetalnih opažanj o vseh ustreznih podatkih o zarodu.
Numerical results should be evaluated by an appropriate statistical method using the litter as the unit for data analysis.
Numerični rezultati se ocenijo z ustrezno statistično metodo z uporabo zaroda kot enote za podatkovno analizo.
A generally accepted statistical method should be used; the statistical methods should be selected as part of the design of the study and should be justified.
Uporabi se splošno sprejeta statistična metoda, statistične metode je treba določiti pri načrtovanju študije in jih utemeljiti.
Data from animals that do not survive to the scheduled kill should also be reported.
Sporočajo se tudi podatki o živalih, ki ne preživijo do predvidene usmrtitve.
These data may be included in group means where relevant.
Ti podatki se lahko po potrebi vključijo v skupinske podatke.
Relevance of the data obtained from such animals, and therefore inclusion or exclusion from any group mean(s), should be justified and judged on an individual basis.
Ustreznost podatkov, dobljenih o teh živalih in vključitev ali izključitev iz katerih koli skupinskih podatkov, je treba utemeljiti ali presoditi na individualni podlagi.
maternal and embryo/foetal test results, including the evaluation of the relationship, or lack thereof, between the exposure of the animals to the test substance and the incidence and severity of all findings,
rezultate preskusa pri materi in embriu/fetusu, vključno z ovrednotenjem razmerja ali njegove odsotnosti med izpostavljenostjo živali preskusni snovi in pojavom ter resnostjo vseh ugotovitev,
criteria used for categorising foetal external, soft tissue, and skeletal alterations if categorisation has been done,
merila, uporabljena za kategorizacijo zunanjih sprememb fetusa ter sprememb mehkega tkiva in skeleta, če je bila kategorizacija opravljena,
when appropriate, historical control data to enhance interpretation of study results,
kadar je primerno, pretekle kontrolne podatke za izboljšanje razlage rezultatov študije,
the numbers used in calculating all percentages or indices,
številke, uporabljene pri izračunu vseh odstotkov ali kazalnikov,
adequate statistical analysis of the study findings, when appropriate, which should include sufficient information on the method of analysis, so that an independent reviewer/statistician can re-evaluate and reconstruct the analysis.
ustrezne statistične analize ugotovitev študije, če je to primerno, ki naj vključujejo dovolj informacij o metodi analize, tako da lahko neodvisni ocenjevalec/statistik ponovno ovrednoti in obnovi analizo,
In any study which demonstrates the absence of any toxic effects, further investigations to establish absorption and bioavailability of the test substance should be considered.
Pri kateri koli študiji, ki dokaže odsotnost katerega koli toksičnega učinka, je treba razmisliti o nadaljnjih raziskavah za določitev absorpcije in biološke razpoložljivosti preskusne snovi.
A prenatal developmental toxicity study will provide information on the effects of repeated exposure to a substance during pregnancy on the dams and on the intrauterine development of their progeny.
Študija strupenosti za predrojstveni razvoj zagotovi informacije o učinkih ponovne izpostavljenosti tej snovi med brej ostjo na matere in razvoj njihovih potomcev v maternici.
The results of the study should be interpreted in conjunction with the findings from subchronic, reproduction, toxicokinetic and other studies.
Rezultate študije je treba razlagati skupaj z ugotovitvami subkroničnih, reprodukcijskih, toksikokinetičnih in drugih študij.
Since emphasis is placed both on general toxicity in terms of maternal toxicity and on developmental toxicity endpoints, the results of the study will allow to a certain extent for the discrimination between developmental effects occurring in the absence of general toxicity and those which are only induced at levels that are also toxic to the maternal animal (27).
Ker je poudarek tako na splošni toksičnosti v smislu toksičnosti pri materi kot na ciljnih učinkih strupenosti za razvoj, rezultati študije do določene mere omogočajo razlikovanje med razvojnimi učinki, ki se pojavijo v odsotnosti splošne toksičnosti in učinki, ki so doseženi samo na stopnjah, ki so strupene tudi za mater (27).
The test report must include the following specific information:
Poročilo o preskusu mora vsebovati naslednje posebne informacije:
physical nature and, where relevant, physiochemical properties,
fizikalno stanje in, kjer je to ustrezno, fizikalno-kemijske lastnosti,
identification including CAS number if known/established,
identifikacijo, vključno s številko po CAS, če je znana/določena,
purity.
čistost.
environmental conditions,
okoljske razmere,
Maternal toxic response data by dose, including but not limited to:
Podatki o toksičnem učinkovanju pri materi po odmerku, ki vključujejo, vendar niso omejeni na:
the number of animals at the start of the test, the number of animals surviving, the number pregnant, and the number aborting, number of animals delivering early,
število živali na začetku preskusa, število preživelih živalih, število brejih in število živali, ki splavijo ali kotijo predčasno,
day of death during the study or whether animals survived to termination,
dan smrti med študijo ali če živali preživijo do konca,
data from animals that do not survive to the scheduled kill should be reported but not included in the inter-group statistical comparisons,
podatki o živalih, ki ne preživijo do predvidene usmrtitve, se sporočijo, vendar se ne vključijo v medskupinske statistične primerjave,
day of observation of each abnormal clinical sign and its subsequent course,
dan opazovanj a vsakega nenormalnega kliničnega znaka in poznejšega poteka,
body weight, body weight change and gravid uterine weight, including, optionally, body weight change corrected for gravid uterine weight,
telesno maso, spremembo telesne mase in maso gravidne maternice, vključno, po izbiri, s spremembo telesne mase popravljeno za maso gravidne maternice,
food consumption and, if measured, water consumption,
porabo hrane in porabo vode, če je izmerjena,
necropsy findings, including uterine weight,
ugotovitve obdukcije, vključno z maso maternice,
NOAEL values for maternal and developmental effects should be reported.
treba je poročati o vrednostih brez opaznih škodljivih učinkov pri materi in o razvojnih učinkih.
Developmental endpoints by dose for litters with implants, including:
Ciljni učinki za razvoj po odmerku na zarod z vsadki, ki vključujejo:
number of corpora lutea,
število rumenih telesc,
number of implantations, number and percent of live and dead foetuses and resorptions,
število vgnezditev, število in odstotek živih in mrtvih fetusov in resorpcij,
number and percent of pre- and post-implantation losses.
število in odstotek izgub pred vgnezditvijo in po njej.
Developmental endpoints by dose for litters with live foetuses, including:
Ciljni učinki za razvoj po odmerku na zarod z živimi fetusi, ki vključujejo:
number and percent of live offspring,
število in odstotek živih potomcev,
sex ratio,
razmerje spolov,
foetal body weight, preferably by sex and with sexes combined,
fetalna telesna masa, če je mogoče po spolu in skupno,
external, soft tissue, and skeletal malformations and other relevant alterations,
zunanje deformnosti in deformnosti mehkega tkiva in skeleta ter druge ustrezne spremembe,
criteria for categorisation if appropriate,
merila za kategorizacijo, če je primerno,
total number and percent of foetuses and litters with any external, soft tissue, or skeletal alteration, as well as the types and incidences of individual anomalies and other relevant alterations.
skupno število in odstotek fetusov in zaroda z zunanjo spremembo, spremembo mehkega tkiva ali skeleta, pa tudi vrste in pojavnost posameznih nepravilnosti in druge ustrezne spremembe.
Naunyn-Schmeidebergs Archiv fur Pharmakologie und Experimentelle Pathologie, 247, 367.
Naunyn-Schmeidebergs Archiv für Pharmakologie undExperimentelle Pathologie 247:367.
Edwards, J.A., (1968) The external Development of the Rabbit and Rat Embryo.
Edwards, J. A. (1968) The external Development of the Rabbit and Rat Embryo.
Inouye, M. (1976) Differential Staining of Cartilage and Bone in Fetal Mouse Skeleton by Alcian Blue and Alizarin Red S. Congenital Anomalies 16, p. 171-173.
Inouye, M. (1976) Differential Staining of Cartilage and Bone in Fetal Mouse Skeleton by Alcian Blue and Alizarin Red S. Congenital Anomalies 16, 171–173.
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Congenital Anomalies 32, 381-391.
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Teratology 11, 313–320.
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Toxicology and Applied Pharmacology 9, 398–408.
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Teratology 8, 309–316.
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Teratology 46, 169–181.
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The test substance is administered normally seven days per week, by an appropriate route, to several groups of experimental animals, one dose per group, for a major portion of their lifespan.
Preskusna snov se običajno daje sedem dni na teden na ustrezen način nekaj skupinam preskusnih živali, in sicer po en odmerek na skupino, večji del življenjske dobe živali.
During and after exposure to the test substance, the experimental animals are observed daily to detect signs of toxicity, particularly the development of tumours.
Med in po izpostavljenosti preskusni snovi se živali opazujejo dnevno, da bi se odkrilo znake strupenosti, zlasti razvoj tumorjev.
For rodents at least 100 animals (50 female and 50 male) should be used at each dose level and concurrent control group.
Pri glodalcih je treba za vsako velikost odmerka in sočasno kontrolno skupino uporabiti najmanj 100 živali (50 samic in 50 samcev).
The highest dose level should elicit signs of minimal toxicity, such as a slight depression of bodyweight gain (less than 10 %), without substantially altering the normallifespan due to effects other than tumours.
Najvišja velikost odmerka bi morala sprožiti znake minimalne strupenosti, kot je rahel zastoj pri pridobivanju telesne mase (manj kot 10 %), ne da bi se pri tem bistveno spremenila normalna življenjska doba zaradi drugih učinkov, razen tumorjev.
The lowest dose level should not interfere with normal growth, development and longevity of the animal or produce any indication of toxicity.
Najnižja velikost odmerka ne sme vplivati na normalno rast, razvoj in življenjsko dobo živali ali povzročiti kakršne koli znake strupenosti.
In general, this should not be lower than 10 % of the high dose.
Na splošno ta ne sme biti nižja od 10 % visokega odmerka.
In special circumstances, such as in inhalation studies involving aerosols or the use of an emulsifier of uncharacterised biological activity in oral studies, an additional control group which is not exposed to the vehicle should be used.
V posebnih okoliščinah, kot so inhalacijske študije z aerosoli ali uporaba emulgatorjev v oralnih študijah, katerih biološka aktivnost ni znana, je treba uporabiti dodatno kontrolno skupino, ki ni izpostavljena nosilcu.
The three main routes of administration are oral, dermal and inhalation.
Trije glavni načini dajanja so oralni, dermalni in inhalacijski.