natgillin/translations-raw huggingface dataset:
However, based on a weight of evidence, it may suffice to terminate the litters on PND 4 rather than follow them to weaning or beyond.
Pri živalih iz kohorte 1B se stehtajo in do vklapljanja v blok obdelajo naslednji organi in tkiva:
TERMINAL OBSERVATIONS
nožnica (nestehtana),
Clinical biochemistry/Haematology
maternica z materničnim vratom,
Systemic effects should be monitored in P animals.
jajčniki,
Fasted blood samples from a defined site are taken from 10 randomly-selected P males and females per dose group at termination, stored under appropriate conditions and subjected to partial or full-scale haematology, clinical biochemistry, assay of T4 and TSH or other examinations suggested by the known effect profile of the test chemical (see OECD Guidance Document 151(40)).
moda (vsaj eno),
The following haematological parameters should be examined:
obmodki,
haematocrit, haemoglobin concentration, erythrocyte count, total and differential leukocyte count, platelet count and blood clotting time/potential.
semenski mešički in koagulacijske žleze,
Investigations of plasma or serum should include:
prostata,
glucose, total cholesterol, urea, creatinine, total protein, albumin and at least two enzymes indicative of hepatocellular effects (such as alanine aminotranferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase and sorbitol dehydrogenase).
hipofiza,
Measurements of additional enzymes and bile acids may provide useful information under certain circumstances.
opredeljeni tarčni organi.
In addition, blood from all animals may be taken and stored for possible analysis at a later time to help clarify equivocal effects or to generate internal exposure data.
Histopatološke preiskave pri kohorti 1B se izvedejo, če so rezultati iz kohorte 1A dvoumni, ali v primeru domnevnih strupenih snovi za razmnoževanje ali domnevnih povzročiteljev endokrinih motenj.
If a second mating of P animals is not intended, the blood samples are obtained just prior to, or as part of, the procedure at scheduled sacrifice.
Kohorti 2A in 2B:
In the case animals are retained, blood samples should be collected a few days before the animals are mated for the second time.
Preskušanje razvojne nevrotoksičnosti (21. ali 22. poporodni dan in odrasli potomci).
Unless existing data from repeated-dose studies indicate that the parameter is not affected by the test chemical, urinalysis should be performed prior to termination and the following parameters evaluated:
Živali iz kohorte 2A je treba po vedenjskem preskušanju usmrtiti, zabeležiti težo možganov in izvesti popolne nevrohistopatološke preiskave zaradi ocene nevrotoksičnosti.
appearance, volume, osmolality or specific gravity, pH, protein, glucose, blood and blood cells, cell debris.
Živali iz kohorte 2B se usmrtijo 21. ali 22. poporodni dan, zabeleži se teža možganov in izvede mikroskopski pregled možganov za oceno nevrotoksičnosti.
Urine may also be collected to monitor excretion of test chemical and/or metabolite(s).
Fiksiranje s perfuzijo je zahtevano pri živalih iz kohorte 2A in neobvezno pri živalih iz kohorte 2B, kot to določa preskusna metoda B.53 (35).
Systemic effects should also be monitored in F1 animals.
Teža organov in shranjevanje tkiv – odstavljeni mladiči F1
Fasted blood samples from a defined site are taken from 10 randomly selected cohort 1A males and females per dose group at termination, stored under appropriate conditions and subjected to standard clinical biochemistry, including the assessment of serum levels for thyroid hormones (T4 and TSH), haematology (total and differential leukocyte plus erythrocyte counts) and urinalysis assessments.
Mladiči, ki niso izbrani za kohorte, vključno s spački, so po odstavitvi, na 22. poporodni dan, usmrčeni, razen če so na podlagi rezultatov potrebne nadaljnje preiskave živih živali.
The surplus pups at PND 4 are subject to gross necropsy and consideration given to measuring serum thyroid hormone (T4) concentrations.
Na usmrčenih mladičih se izvede makroskopska obdukcija in ocenijo razmnoževalni organi, kakor je opisano v odstavkih 62 in 63.
If necessary, neonatal (PND 4) blood can be pooled by litters for biochemical/thyroid hormone analyses.
Pri največ 10 mladičih na spol na skupino iz čim več zarodov je treba stehtati možgane, vranico in priželjc ter jih shraniti pod ustreznimi pogoji.
Blood is also collected for T4 and TSH analysis from weanlings subject to gross necropsy on PND 22 (F1 pups not selected for cohorts).
Poleg tega se lahko tkiva mlečnih žlez teh mladičev moškega in ženskega spola shranijo za nadaljnjo mikroskopsko analizo [13] (glej Smernico OECD št. 151 (40)).
Sperm parameters
Večje nepravilnosti in tarčna tkiva je treba shraniti za morebiten histološki pregled.
Sperm parameters should be measured in all P generation males unless there is existing data to show that sperm parameters are unaffected in a 90-day study.
Histopatologija – starševske (P) živali
Examination of sperm parameters should be performed in all cohort 1A males.
Poleg tega se histopatološko ovrednotijo razmnoževalni organi vseh živali, za katere se domneva zmanjšana plodnost, npr. pri tistih, ki se niso mogli spariti, spočeti, zaploditi ali skotiti zdravih potomcev, ali pri katerih so bili prizadeti cikličnost pojatev ali število, gibljivost ali morfologija semena, in vse makroskopske poškodbe.
At termination, testis and epididymis weights are recorded for all P and F1 (cohort 1A) males.
Histopatologija – živali F1
At least one testis and one epididymis are reserved for histopathological examination.
Živali iz kohorte 1
The remaining epididymis is used for enumeration of cauda epididymis sperm reserves (16) (17).
Popolni histopatološki pregled iz odstavkov 62 in 63 se opravi za vse odrasle živali iz skupin z velikim odmerkom in kontrolnih skupin iz kohorte 1A.
In addition, sperm from the cauda epididymis (or vas deferens) is collected using methods that minimise damage for evaluation of sperm motility and morphology (18).
Iz vsakega legla se uporabi vsaj 1 mladič vsakega spola.
Sperm motility can either be evaluated immediately after sacrifice or recorded for later analysis.
Vse makroskopske poškodbe ter organe in tkiva, pri katerih so vidne spremembe zaradi tretiranja, je treba pregledati tudi pri vseh živalih iz skupin z manjšimi odmerki za pomoč pri določanju NOAEL.
The percentage of progressively motile sperm could be determined either subjectively or objectively by computer-assisted motion analysis (19) (20) (21) (22) (23) (24).
Za vrednotenje pred- in poporodno povzročenih učinkov na limfoidne organe je treba poleg histopatološkega vrednotenja priželjca, vranice in nadledvičnih žlez, ki se opravi pri vseh živalih iz kohorte 1A, pri 10 samcih in 10 samicah iz kohorte 1A opraviti tudi histopatološko vrednotenje na odvzetih bezgavkah in kostnem mozgu.
For the evaluation of sperm morphology, an epididymal (or vas deferens) sperm sample should be examined as fixed or wet preparations (25) and at least 200 spermatozoa per sample classified as either normal (both head and midpiece/tail appear normal) or abnormal.
Pri razmnoževalnih in endokrinih tkivih vseh živali iz kohorte 1B, obdelanih do vklapljanja v blok v skladu z odstavkom 66, je treba v primeru domnevnih strupenih snovi za razmnoževanje ali domnevnih povzročiteljev endokrinih motenj opraviti histopatološke preglede.
Examples of morphologic sperm abnormalities would include fusion, isolated heads, and misshapen heads and/or tails (26).
Živali iz kohorte 1B se histološko pregledajo tudi v primeru, da so rezultati iz kohorte 1A dvoumni.
Misshapen or large sperm heads may indicate defects in spermiation.
Jajčniki odraslih samic bi morali vsebovati začetne in rastoče folikle, pa tudi rumena telesca;
If sperm samples are frozen, smears fixed and images for sperm motility analysis recorded at the time of necropsy (27), subsequent analysis may be restricted to control and high-dose males.
histopatološki pregled bi zato moral biti namenjen količinskemu vrednotenju začetnih in majhnih rastočih foliklov ter rumenih telesc pri samicah F1;
However, if treatment-related effects are observed, the lower dose groups should also be evaluated.
število živali, izbira rezine jajčnika in velikost vzorca rezine morajo biti statistično ustrezni za uporabljeni postopek vrednotenja.
Gross necropsy
Štetje foliklov se lahko najprej izvede na živalih iz kontrolnih skupin in skupin z velikim odmerkom, v primeru škodljivih učinkov pri slednjih pa je treba proučiti tudi nižje odmerke.
At the time of termination or premature death, all P and F1 animals are necropsied and examined macroscopically for any structural abnormalities or pathological changes.
Pregled mora vključevati štetje števila začetnih foliklov, ki se lahko kombinirajo z majhnimi rastočimi folikli, za primerjavo tretiranih in kontrolnih jajčnikov (glej Smernico OECD št. 151) (40)).
Special attention should be paid to the organs of the reproductive system.
Oceno rumenih telesc je treba izvesti vzporedno s preskušanjem cikličnosti pojatev, tako da se lahko faza cikla upošteva pri vrednotenju.
Pups that are humanely killed in a moribund condition and dead pups should be recorded and, when not macerated, examined for possible defects and/or cause of death and preserved.
Preveriti je treba, ali so se jajcevod, maternica in nožnica ustrezno razvili.
For adult P and F1 females, a vaginal smear is examined on the day of necropsy to determine the stage of the oestrous cycle and allow correlation with histopathology in reproductive organs.
Pri samcih F1 se izvedejo podrobni histopatološki pregledi mod, da bi se ugotovili učinki na diferenciacijo in razvoj mod ter na spermatogenezo, povezani s tretiranjem (38).
The uteri of all P females (and F1 females, if applicable) are examined for the presence and number of implantation sites, in a manner which does not compromise histopathological evaluation.
Če je mogoče, je treba pregledati rezine mrežja mod.
Organ weight and tissue preservation — P and F1 adult animals
Preveriti je treba, ali so se glava, telo in rep obmodkov in semenovod ustrezno razvili, pa tudi parametre za te organe, zahtevane za starševske (P) samce.
At the time of termination, body weights and wet weights of the organs listed below from all P animals and all F1 adults, from relevant cohorts (as outlined below), are determined as soon as possible after dissection to avoid drying.
Živali iz kohorte 2
These organs should then be preserved under appropriate conditions.
Za vse skupine z velikimi odmerki in kontrolne skupine živali iz kohorte 2A se po končanem preskušanju za nevrološko-vedenjske motnje (po 75. poporodnem dnevu, vendar ne po 90. poporodnem dnevu) opravijo nevrohistopatološki pregledi pri obeh spolih.
Unless specified otherwise, paired organs can be weighed individually or combined, consistent with the typical practice of the performing laboratory.
Histopatološki pregled možganov se pri vseh skupinah z velikimi odmerki in kontrolnih skupinah živali kohorte 2B pri obeh spolih opravi na 21. ali 22. poporodni dan.
Uterus (with oviducts and cervix), ovaries
Organe ali tkiva, pri katerih so vidne spremembe zaradi tretiranja, je prav tako treba pregledati pri vseh živalih iz skupin z manjšimi odmerki za pomoč pri določanju NOAEL.
Testes, epididymides (total and cauda for the samples used for sperm counts)
Pri živalih iz kohort 2A in 2B se pregleda več rezin možganov, pri čemer se pregledajo vohalni bulbus, možganska skorja, hipokampus, bazalni gangliji, talamus, hipotalamus, srednji možgani (tectum, tegmentum in možganski pedunkli), možgansko deblo in mali možgani.
Prostate (dorsolateral and ventral parts combined).
Samo pri živalih iz kohorte 2A se pregledajo oči (mrežnica in vidni živec) ter vzorci perifernega živca, mišice in hrbtenjače.
Care should be exercised when trimming the prostate complex to avoid puncture of the fluid filled seminal vesicles.
Vsi nevrohistološki postopki morajo biti v skladu s preskusno metodo B.53 (35).
In the event of a treatment-related effect on total prostate weight, the dorsolateral and ventral segments should be carefully dissected after fixation, and weighed separately.
Morfometrična (kvantitativna) vrednotenja je treba opraviti na reprezentativnih območjih možganov (homolognih rezinah, skrbno izbranih na podlagi zanesljivih mikroskopskih znakov) in lahko vključujejo linearne in/ali površinske meritve določenih predelov možganov.
Seminal vesicles with coagulating glands and their fluids (as one unit)
Da bi se izbrala najbolj homologna in reprezentativna rezina za določen predel možganov, ki se bo vrednotil, je treba vzeti vsaj tri zaporedne rezine pri vsakem znaku (ravni).
Brain, liver, kidneys, heart, spleen, thymus, pituitary, thyroid (post-fixation), adrenal glands and known target organs or tissues.
Nevropatolog bi moral ustrezno presoditi, ali so rezine, pripravljene za meritev, homologne z drugimi v vzorcu in torej primerne za uporabo, ker se lahko zlasti linearne meritve spreminjajo na relativno kratki razdalji (28).
In addition to the organs listed above, samples of peripheral nerve, muscle, spinal cord, eye plus optic nerve, gastrointestinal tract, urinary bladder, lung, trachea (with thyroid and parathyroid attached), bone marrow, vas deferens (males), mammary gland (males and females) and vagina should be preserved under appropriate conditions.
Nehomologne rezine se ne smejo uporabiti.
Cohort 1A animals have all organs weighed and preserved for histopathology.
Cilj je vzorčenje vseh živali, ki so za to namenjene (10/spol/velikost odmerka), vendar lahko zadošča tudi manjše število živali.
For the investigation of pre- and postnatally induced immunotoxic effects, 10 male and 10 female cohort 1A animals from each treatment group (1 male or 1 female per litter; all litters represented by at least 1 pup; randomly selected) will be subject to the following at termination:
Vzorci, manjši od 6 živali/spol/velikost odmerka, na splošno ne zadoščajo za namene te preskusne metode.
weighing of the lymph nodes associated with and distant from the route of exposure (in addition to the weight of the adrenal glands, the thymus and the spleen, already performed in all cohort 1A animals)
S stereologijo se lahko opredelijo s tretiranjem povezani učinki na parametre, kot je količina ali število celic za določene nevroanatomske predele.
splenic lymphocyte subpopulation analysis (CD4+ and CD8+ T lymphocytes, B lymphocytes, and natural killer cells) using one half of the spleen, the other half of the spleen being preserved for histopathological evaluation,
Vsi vidiki priprave vzorcev tkiva, od fiksacije tkiva do seciranja vzorcev tkiva, obdelave tkiva in barvanja preparatov, bi morali biti načrtovani uravnoteženo, tako da vsaka serija vsebuje reprezentativne vzorce vsake skupine z odmerkom.
Analysis of splenic lymphocyte subpopulations in non-immunised (cohort 1A) animals will determine if exposure is related to a shift in the immunological steady state distribution of “helper” (CD4+) or cytotoxic (CD8+) thymus-derived lymphocytes or natural killer (NK) cells (rapid responses to neoplastic cells and pathogens).
Pri uporabi morfometrične ali stereološke analize je treba možgansko tkivo vstaviti v ustrezen medij pri vseh velikostih odmerka hkrati, da se ne bi pojavili artefakti zaradi skrčenja, povezani z dolgotrajno hrambo v fiksativu.
Cohort 1B animals should have the following organs weighed and corresponding tissues processed to the block stage:
Podatki se sporočajo posamično in se povzamejo v obliki tabele.
Vagina (not weighed)
Kadar je to mogoče, se za vsako skupino in vsako generacijo sporočijo naslednji podatki:
Uterus with cervix
število živali na začetku preskusa, število živali, najdenih poginulih ali usmrčenih iz humanih razlogov med preskusom, čas katere koli smrti ali humane usmrtitve, število plodnih živali, število brejih samic, število samic, ki so skotile zarod, in število živali, ki kažejo znake strupenosti.
Ovaries
Sporočiti je treba opis strupenosti, vključno s časom njenega začetka, trajanja in resnosti.
Testes (at least one)
Številčni rezultati se morajo oceniti z ustrezno in sprejeto statistično metodo.
Epididymides
Statistične metode je treba določiti pri načrtovanju študije; ustrezno morajo obravnavati nenormalne podatke (npr. podatke štetja), okrnjene podatke (npr. omejen čas opazovanja), odvisnost (npr. učinki na zarod in ponovljeni ukrepi) in neenake variance.
Seminal vesicles and coagulating glands
Posplošeni linearni mešani modeli in modeli odziva na odmerek obsegajo obsežen sklop analitičnih orodij, ki so morda primerni za podatke, pridobljene na podlagi te preskusne metode.
Prostate
Poročilo mora vključevati dovolj informacij o metodi analize in uporabljenem računalniškem programu, tako da lahko neodvisni ocenjevalec/statistik ovrednoti/ponovno ovrednoti analizo.
Pituitary
Vrednotenje rezultatov
Histopathology in cohort 1B would be conducted if results from cohort 1A are equivocal or in cases of suspected reproductive or endocrine toxicants.
Vrednotenje vključuje razmerje ali odsotnost razmerja med odmerkom ter navzočnostjo, pojavom in resnostjo anomalij, vključno z makroskopskimi poškodbami.
Cohorts 2A and 2B:
Oceniti je treba tudi tarčne organe, plodnost, klinične anomalije, zmogljivost razmnoževanja in produkcije zaroda, spremembe telesne teže, učinke na smrtnost ter druge strupene učinke in učinke na razvoj.
Developmental neurotoxicity testing (PND 21 or PND 22 and adult offspring).
Posebno pozornost je treba nameniti spremembam, omejenim na en spol.
Cohort 2A animals are terminated after behavioural testing, with brain weight recorded and full neurohistopathology for purposes of neurotoxicity assessment.
Pri vrednotenju rezultatov je treba upoštevati fizikalno-kemijske lastnosti preskusne kemikalije in, če so na voljo, podatke o toksikokinetiki, vključno s prenosom prek posteljice in izločanjem mleka.
Cohort 2B animals are terminated on PND 21 or PND 22, with brain weight recorded and microscopic examination of the brain for purposes of neurotoxicity assessment.
Poročilo o preskusu naj vsebuje naslednje informacije, pridobljene s to študijo s pomočjo starševskih (P) živali, živali F1 in živali F2 (kot je ustrezno):
Perfusion fixation is required for cohort 2A animals and optional for cohort 2B animals, as provided in test method B.53 (35).
vse zadevne razpoložljive informacije o kemikaliji, toksikokinetičnih in toksikodinamičnih lastnostih preskusne kemikalije,
Organ weight and tissue preservation — F1 weanlings
identifikacijske podatke,
The pups not selected for cohorts, including runts, are terminated after weaning, on PND 22, unless the results indicate the need for further in-life investigations.
čistoto.
Terminated pups are subjected to gross necropsy including an assessment of the reproductive organs, as described in paragraphs 62 and 63.
utemeljitev izbire nosilca, če ta ni voda.
For up to 10 pups per sex per group, from as many litters as possible, brain, spleen, and thymus should be weighed and retained under appropriate conditions.
uporabljeno vrsto/sev,
In addition, mammary tissues for these male and female pups may be preserved for further microscopic analysis [13] (see OECD Guidance Document 151(40)).
število, starost in spol živali,
Gross abnormalities and target tissues should be saved for possible histological examination.
izvor, pogoje nastanitve, hrano, material za izdelavo gnezda itd.,
Histopathology — P animals
težo posameznih živali na začetku preskusa,
Full histopathology of the organs listed in paragraphs 62 and 63 is performed for all high-dose and control P animals.
podatke o vaginalnem brisu za starševske (P) samice pred pričetkom tretiranja (če so bili podatki takrat zbrani),
Organs demonstrating treatment-related changes should also be examined in all animals at the lower dose groups to aid in determining a NOAEL.
evidenco parjenja starševske (P) generacije z navedbo samca in samice, ki sta se parila, in uspešnost parjenja,
Additionally, reproductive organs of all animals suspected of reduced fertility, e.g. those that failed to mate, conceive, sire, or deliver healthy offspring, or for which oestrous cyclicity or sperm number, motility, or morphology were affected, and all gross lesions should be subjected to histopathological evaluation.
evidenco o leglu izvora za odrasle živali generacije F1.
Histopathology — F1 animals
utemeljitev izbire velikosti odmerka,
Cohort 1 animals
podatke o sestavi preskusne kemikalije/pripravi hrane, doseženih koncentracijah,
Full histopathology of the organs listed in paragraphs 62 and 63 is performed for all high-dose and control adult cohort 1A animals.
stabilnost in homogenost pripravka v nosilcu (npr. prehrani, pitni vodi), v krvi in/ali mleku pod pogoji uporabe in hrambe med uporabami,
All litters should be represented by at least 1 pup per sex.
podrobne podatke o dajanju preskusne kemikalije,
Organs and tissues demonstrating treatment-related changes and all gross lesions should also be examined in all animals in the lower dose groups to aid in determining a NOAEL.
pretvorbo koncentracije preskusne kemikalije v hrani/pitni vodi (ppm) v dejanski odmerek (mg/kg telesne teže/dan), če je primerno,
For the evaluation of pre- and postnatally induced effects on lymphoid organs also the histopathology on the collected lymph nodes and bone marrow should be evaluated of 10 male and 10 female cohort 1A animals next to histopathological evaluation of the thymus, spleen, and the adrenal glands already performed in all 1A animals.
podrobne podatke o kakovosti hrane in vode (vključno s podatki o sestavi prehrane, če so na voljo),
Reproductive and endocrine tissues from all cohort 1B animals, processed to the block stage as described in paragraph 66, should be examined for histopathology in cases of suspected reproductive or endocrine toxicants.
podroben opis postopkov randomizacije za izbiro mladičev za izločitev in dodelitev mladičev v preskusne skupine,
Cohort 1B should also undergo histological examination if results from cohort 1A are equivocal.
okoljske pogoje,
Ovaries of adult females should contain primordial and growing follicles, as well as corpora lutea;
seznam osebja, ki je sodelovalo v študiji, vključno s strokovno usposobljenostjo.
therefore, a histopathological examination should be aimed at detecting a quantitative evaluation of primordial and small growing follicles, as well as corpora lutea, in F1 females;
Rezultati (povzetek in posamični podatki po spolu in odmerku):
the number of animals, ovarian section selection, and section sample size should be statistically appropriate for the evaluation procedure used.
porabo hrane in porabo vode, če je na voljo, izkoristek hrane (prirast telesne teže na gram zaužite hrane, razen za obdobje sobivanja in med laktacijo) in porabo preskusne kemikalije (za dajanje s hrano/pitno vodo) za starševske (P) živali in živali F1,
Follicular enumeration may first be conducted on control and high-dose animals, and in the event of an adverse effect in the latter, lower doses should be examined.
podatke o absorpciji (če so na voljo),
Examination should include enumeration of the number of primordial follicles, which can be combined with small growing follicles, for comparison of treated and control ovaries (see OECD Guidance Document 151(40)).
podatke o telesni teži za starševske (P) živali,
Corpora lutea assessment should be conducted in parallel with oestrous cyclicity testing so that the stage of the cycle can be taken into account in the assessment.
podatke o telesni teži za izbrane živali F1 po odstavitvi,
Oviduct, uterus and vagina are examined for appropriate organ-typic development.
čas smrti med študijo oziroma ali podatek o tem, da so živali preživele do zaključka,
Detailed testicular histopathology examinations are conducted on the F1 males in order to identify treatment-related effects on testis differentiation and development and on spermatogenesis (38).
vrsto, resnost in trajanje kliničnih opažanj (s podatki o reverzibilnosti),
When possible, sections of the rete testis should be examined.
podatke hematoloških preskusov, analize urina in podatke meritev na področju klinične kemije, vključno s TSH in T4,