natgillin/translations-raw huggingface dataset:
Caput, corpus, and cauda of the epididymis and the vas deferens are examined for appropriate organ-typic development, as well as for the parameters required for the P males.
fenotipsko analizo vraničnih celic (celic T, B, NK),
Cohort 2 animals
celularnosti kostnega mozga,
Neurohistopathology is performed for all high-dose and control cohort 2A animals per sex following completion of neurobehavioral testing (after PND 75, but not to exceed PND 90).
podatke o odzivu na strupenost,
Brain histopathology is performed for all high-dose and control cohort 2B animals per sex on PND 21 or PND 22.
število starševskih (P) samic in samic F1 z normalnim ali nenormalnim pojatvenim ciklom in trajanje cikla,
Organs or tissues demonstrating treatment-related changes should also be examined for the animals in the lower dose groups to aid in determining a NOAEL.
čas do parjenja (predkoitalni interval, število dni med parjenjem in oploditvijo),
For cohort 2A and 2B animals, multiple sections are examined from the brain to allow examination of olfactory bulbs, cerebral cortex, hippocampus, basal ganglia, thalamus, hypothalamus, mid-brain (thecum, tegmentum, and cerebral peduncles), brain-stem and cerebellum.
strupene ali druge učinke na razmnoževanje, vključno s številom in odstotkom živali, ki so se sparile, bile breje, so skotile in dosegle laktacijo, odstotkom samcev, ki so oplodili samico, in samic z znaki distocije/podaljšano ali zahtevno kotitvijo,
For cohort 2A only, the eyes (retina and optic nerve) and samples of peripheral nerve, muscle and spinal cord are examined.
trajanje brejosti in, če so podatki na voljo, kotitve,
All neurohistological procedures should be consistent with test method B.53 (35).
število vgnezditev, velikost zaroda in odstotek mladičev moškega spola,
Morphometric (quantitative) evaluations should be performed on representative areas of the brain (homologous sections carefully selected based on reliable microscopic landmarks) and may include linear and/or areal measurements of specific brain regions.
število in odstotek izgub po vgnezditvi, živorojenih in mrtvorojenih živali,
At least three consecutive sections should be taken at each landmark (level) in order to select the most homologous and representative section for the specific brain area to be evaluated.
podatke o teži zaroda in posameznih mladičev (samcev, samic in obeh spolov), število spačkov, če je ugotovljeno,
The neuropathologist should exercise appropriate judgment as to whether sections prepared for measurement are homologous with others in the sample set and therefore suitable for inclusion, since linear measurements in particular may change over a relatively short distance (28).
število mladičev z večjimi vidnimi anomalijami,
Non-homologous sections should not be used.
strupene ali druge učinke na potomce, poporodno rast, sposobnost preživetja itd.,
While the objective is to sample all animals reserved for this purpose (10/sex/dose level), smaller numbers may still be adequate.
podatke o fizičnih znakih pri mladičih in druge podatke o poporodnem razvoju,
However, samples from fewer than 6 animals/sex/dose level would generally not be considered sufficient for the purposes of this test method.
podatke o spolnem zorenju živali F1,
Stereology may be used to identify treatment-related effects on parameters such as volume or cell number for specific neuroanatomic regions.
podatke o opazovanju funkcij pri mladičih in odraslih, kot je primerno,
All aspects of the preparation of tissue samples, from tissue fixation, through the dissection of tissue samples, tissue processing, and staining of slides, should employ a counterbalanced design, such that each batch contains representative samples from each dose group.
telesno težo ob usmrtitvi in podatke o absolutni in relativni teži organov za starševske (P) živali in odrasle živali F1,
When morphometric or stereological analyses are to be used, then brain tissue should be embedded in appropriate media at all dose levels at the same time in order to avoid shrinkage artefacts associated with prolonged storage in fixative.
ugotovitve obdukcije,
Data are reported individually and summarised in tabular form.
natančen opis vseh histopatoloških ugotovitev,
Where appropriate, for each test group and each generation, the following should be reported:
skupno število semena v repu obmodka, odstotek progresivno gibljivega semena, odstotek morfološko normalnega semena in odstotek semena z ugotovljeno posamezno anomalijo za starševske (P) samce in odrasle samce F1,
number of animals at the start of the test, number of animals found dead during the test or killed for humane reasons, time of any death or humane kill, number of fertile animals, number of pregnant females, number of females giving birth to a litter, and number of animals showing signs of toxicity.
število in faze zrelosti foliklov v jajčnikih starševskih (P) samic in samic F1, če je primerno,
A description of the toxicity, including time of onset, duration, and severity should also be reported.
število rumenih telesc v jajčnikih samic F1,
Numerical results should be evaluated by an appropriate, and accepted statistical method.
statistično obdelavo rezultatov, če je to primerno.
The statistical methods should be selected as part of the study design and should appropriately address non-normal data (e.g. count data), censored data (e.g. limited observation time), non-independence (e.g. litter effects and repeated measures), and unequal variances.
Parametri kohorte 2:
Generalised linear mixed models and dose-response models cover a broad class of analytical tools that may be appropriate for the data generated under this test method.
podroben opis postopkov za standardiziranje opažanj in postopkov ter operativne opredelitve za ocenjevanje opažanj,
The report should include sufficient information on the method of analysis and the computer program employed, so that an independent reviewer/statistician can evaluate/re-evaluate the analysis.
seznam vseh uporabljenih preskusnih postopkov in utemeljitev njihove uporabe,
Evaluation of results
podrobnosti o uporabljenih vedenjskih/funkcionalnih, nevropatoloških in morfometričnih postopkih, vključno z informacijami in podrobnostmi o avtomatiziranih napravah,
The findings should be evaluated in terms of the observed effects, including necropsy and microscopic findings.
postopke za umerjanje in zagotavljanje enakovrednosti naprav ter uravnoteženje tretiranih skupin v preskusnih postopkih,
The evaluation includes the relationship, or lack thereof, between the dose and the presence, incidence, and severity of abnormalities, including gross lesions.
kratko utemeljitev, s katero se pojasnijo odločitve na podlagi strokovne presoje,
Target organs, fertility, clinical abnormalities, reproductive and litter performance, body weight changes, mortality and any other toxic and developmental effects should also be assessed.
podrobnosti o vseh vedenjskih/funkcionalnih, nevropatoloških in morfometričnih ugotovitvah po spolu in skupini z odmerkom, vključno s povečanji in zmanjšanji iz kontrolnih skupin,
Special attention should be given to sex-specific changes.
težo možganov,
The physico-chemical properties of the test chemical, and when available, TK data, including placental transfer and milk excretion, should be taken into consideration when evaluating the test results.
morebitne diagnoze na podlagi nevroloških znakov in poškodb, vključno z naravnimi pojavi bolezni ali stanj,
The test report should include the following information obtained in the present study from P, F1 animals and F2 animals (where relevant):
slike vzorčnih ugotovitev,
All relevant available information on the chemical, toxicokinetic and toxicodynamic properties of the test chemical;
slike majhne povečave za ocenjevanje homologije rezin, uporabljenih za morfologijo,
Identification data;
statistično obdelavo rezultatov, vključno s statističnimi modeli, uporabljenimi za analizo podatkov, in rezultate, ne glede na to, ali so bili značilni ali ne,
Purity;
odnos katerih koli drugih strupenih učinkov do sklepne ugotovitve o nevrotoksičnem potencialu preskusne kemikalije, po spolu in skupini z odmerkom,
Justification for choice of vehicle if other than water;
vpliv katerih koli informacij o toksikokinetiki na sklepne ugotovitve,
Species/strain used;
podatke, ki podpirajo zanesljivost in občutljivost preskusne metode (tj. podatke o pozitivni kontroli in pretekle kontrolne podatke),
Number, age and sex of animals;
odnose, če obstajajo, med nevropatološkimi in funkcionalnimi učinki,
Source, housing conditions, diet, nesting materials, etc.;
NOAEL ali primerjalni odmerek za matere in potomce, po spolu in skupini z odmerkom,
Individual weights of animals at the start of the test;
razpravo o celotni razlagi podatkov na podlagi rezultatov, vključno s sklepno ugotovitvijo o tem, ali je kemikalija povzročila razvojno nevrotoksičnost, in NOAEL.
Vaginal smear data for P females before initiation of treatment (if data are collected at that time);
Parametri kohorte 3:
P generation pairing records indicating male and female partner of a mating and mating success;
titre serumskih protiteles IgM (senzibilizacija na SRBC ali KHL) ali vraničnih enot IgM PFC (senzibilizacija na SRBC),
Litter of origin records for adult F1 generation animals;
izvajanje metode TDAR morajo v okviru procesa optimizacije potrditi laboratorij, ki prvič izvaja preskus, in redno (npr. letno) vsi laboratoriji,
Rationale for dose level selection;
razpravo o celotni razlagi podatkov na podlagi rezultatov, vključno s sklepno ugotovitvijo o tem, ali je kemikalija povzročila razvojno imunotoksičnost, in NOAEL.
Details of test chemical formulation/diet preparation, achieved concentrations;
Razprava o rezultatih
Stability and homogeneity of the preparation in the vehicle or carrier (e.g. diet, drinking water), in the blood and/or milk under the conditions of use and storage between uses;
Sklepne ugotovitve, tudi vrednosti brez opaznih škodljivih učinkov pri starših in potomcih
Details of the administration of the test chemical;
Zagotoviti je treba tudi vse informacije, ki niso bile pridobljene med študijo, ampak so uporabne za razlago rezultatov (npr. podobnost učinkov z učinki znanih nevrotoksinov).
Conversion from diet/drinking water test chemical concentration (ppm) to the achieved dose (mg/kg body weight/day), if applicable;
Razlaga rezultatov
Details of food and water quality (including diet composition, if available);
Razširjena enogeneracijska študija strupenosti za razmnoževanje po potrebi zagotavlja informacije o učinkih ponovne izpostavljenosti kemikaliji med vsemi fazami reprodukcijskega cikla.
Detailed description of the randomisation procedures to select pups for culling and to assign pups to test groups;
Študija zlasti zagotavlja informacije o razmnoževalnem sistemu ter o končnih točkah razvoja, rasti, preživetja in delovanja potomcev do 90. poporodnega dne.
Environmental conditions;
Pri razlagi rezultatov je treba upoštevati vse razpoložljive informacije o kemikaliji, vključno s fizikalno-kemijskimi, toksikokinetičnimi in toksikodinamičnimi lastnostmi, razpoložljive zadevne informacije o strukturnih analogih in rezultate iz predhodno izvedenih študij strupenosti s preskusno kemikalijo (npr. akutno strupenost, strupenost po ponovnih aplikacijah, mehanistične študije ter študije za ocenjevanje znatnih kvalitativnih in kvantitativnih razlik med vrstami med presnovnimi lastnostmi in vivo/in vitro).
List of study personnel, including professional training;
Rezultate makroskopske obdukcije in tehtanja organov je treba oceniti v smislu ugotovitev iz drugih študij s ponavljajočimi se odmerki, kadar je to izvedljivo.
Results (summary and individual data by sex and dose):
Zmanjšano rast potomcev je mogoče obravnavati v zvezi z učinkom preskusne kemikalije na sestavo mleka (29).
Food consumption, water consumption if available, food efficiency (body weight gain per gram of food consumed, except for the period of cohabitation and during lactation), and test chemical consumption (for dietary/drinking water administration) for P and F1 animals;
Kohorta 2 (razvojna nevrotoksičnost)
Absorption data (if available);
Rezultate nevrovedenjske in nevropatološke analize je treba razlagati v okviru vseh ugotovitev z analizo, ki temelji na tehtnosti dokazov, in strokovno presojo.
Body weight data for P animals;
V to opredelitev je treba vključiti vrednotenje razvojne nevrotoksičnosti, vključno z epidemiološkimi študijami na ljudeh ali poročili o primerih, in eksperimentalne študije na živalih (npr. podatki o toksikokinetiki, informacije o razmerju med strukturo in aktivnostjo, podatki iz drugih študij strupenosti).
Body weight data for the selected F1 animals postweaning;
Za navodila o razlagi rezultatov o razvojni nevrotoksičnosti glej preskusno metodo B.53 (35) in Tyl et al., 2008 (31).
Time of death during the study or whether animals survived to termination;
Kohorta 3 (razvojna imunotoksičnost)
Nature, severity and duration of clinical observations (whether reversible or not);
V okviru vseh ugotovitev je treba ovrednotiti zaviranje ali krepitev imunskega sistema, kakor je ocenjena s TDAR (protitelesni odziv na osnovi T-celic).
Haematology, urinalysis and clinical chemistry data including TSH and T4;
Pomembnost rezultata odziva protiteles, odvisnega od celic T, lahko podprejo drugi učinki na imunološko povezane kazalnike (npr. celularnost kostnega mozga, teža in histopatološke preiskave limfoidnih tkiv, razporeditev podskupin limfocitov).
Phenotypic analysis of spleen cells (T-, B-, NK-cells);
Učinki, ugotovljeni na podlagi odziva protiteles, odvisnega od celic T, morda ne bodo tako pomembni v primeru drugih ugotovljenih strupenosti pri nizkih koncentracijah izpostavljenosti.
Bone marrow cellularity;
Za pomoč pri razlagi rezultatov o razmnoževanju in nevrotoksičnosti glej Smernico OECD št. 43 (26).
Toxic response data;
Whitby (2006), 'A Tiered Approach to Life Stages Testing for Agricultural Chemical Safety Assessment', Critical Reviews in Toxicology, 36, 69–98.
Number of P and F1 females with normal or abnormal oestrous cycle and cycle duration;
Forsythe (1999), ‚Phytoestrogen Content of Purified Open and Closed Formula Laboratory Animal Diets‘, Lab.
Time to mating (precoital interval, the number of days between pairing and mating);
Sci., 49, 530–536.
Toxic or other effects on reproduction, including numbers and percentages of animals that accomplished mating, pregnancy, parturition and lactation, of males inducing pregnancy, of females with signs of dystocia/prolonged or difficult parturition;
Moser, V.C., I. Walls and T. Zoetis (2005), ‚Direct Dosing of Preweaning Rodents in Toxicity Testing and Research: Deliberations of an ILSI RSI Expert Working Group‘, International Journal of Toxicology, 24, 87–94.
Duration of pregnancy and, if available, parturition;
Goodman (1999), ‚Stimulating Research to Improve the Scientific Basis of Risk Assessment‘, Toxicological Sciences, 49, 1–4.
Numbers of implantations, litter size and percentage of male pups;
Palmer (1995), ‚Detection of Effects on Male Reproduction – a Literature Survey‘, Journal of the American College of Toxicologists, 14, 293–327.
Number and percent of post-implantation loss, live births and stillbirths;
Mangelsdorf, I., J. Buschmann and B. Orthen (2003), ‚Some Aspects Relating to the Evaluation of the Effects of Chemicals on Male Fertility‘, Regulatory Toxicology and Pharmacology, 37, 356–369.
Litter weight and pup weight data (males, females and combined), the number of runts if determined;
‚Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats – overview of the studies‘, Journal of Toxicological Sciences, 25, 1–21.
Number of pups with grossly visible abnormalities;
, ‚Evaluation of Testicular Toxicology: A Synopsis and Discussion of the Recommendations Proposed by the Society of Toxicologic Pathology‘, Birth Defects Research, Part B, 68, 408–415.
Toxic or other effects on offspring, postnatal growth, viability, etc.;
Cooper (2007), ‚The Rodent Estrous Cycle: Characterization of Vaginal Cytology and its Utility in Toxicological Studies‘, Birth Defects Research, Part B, 80 (2), 84–97.
Data on physical landmarks in pups and other postnatal developmental data;
, ‚Cycles and Seasons‘, in C.R.
Data on sexual maturation of F1 animals;
I. Germ Cells and Fertilization, Cambridge, New York.
Data on functional observations in pups and adults, as applicable;
Reynolds (1999), ‚Interpreting the Toxicologic Significance of Alterations in Anogenital Distance: Potential for Confounding Effects of Progeny Body Weights‘, Reproductive Toxicology, 13:
Body weight at sacrifice and absolute and relative organ weight data for the P and adult F1 animals;
Weiner (1977), ‚Preputial Separation as an External Sign of Pubertal Development in the Male Rat‘, Biological Reproduction, 17, 298–303.
Necropsy findings;
, ‚Use of SRBC Antibody Responses for Immunotoxicity Testing‘, Methods, 41, 9–19.
Detailed description of all histopathological findings;
Herzyk (2004), ‚Primary Antibody Response to Keyhole Limpet Hemocyanin in Rat as a Model for Immunotoxicity Evaluation‘, Toxicology, 197, 23–35.
Total cauda epididymal sperm number, percent progressively motile sperm, percent morphologically normal sperm, and percent of sperm with each identified abnormality for P and F1 males;
Gray, L.E., J. Ostby, J. Ferrell, G. Rehnberg, R. Linder, R. Cooper, J. Goldman, V. Slott and J. Laskey (1989), ‚A Dose-Response Analysis of Methoxychlor-Induced Alterations of Reproductive Development and Function in the Rat‘, Fundamental and Applied Toxicology, 12, 92–108.
Numbers and maturational stages of follicles contained in the ovaries of P and F1 females, where applicable;
Killian (1978), ‚Daily Sperm Production and Epididymal Sperm Reserves of Pubertal and Adult Rats‘, Journal of Reproduction and Fertility,54, 103–107.
Enumeration of corpora lutea in the ovaries of F1 females;
Suarez (1991), 'The Method of Sperm Collection Significantly Influences Sperm Motion Parameters Following Ethane Dimethanesulfonate Administration in the Rat'.
Statistical treatment of results, where appropriate;
Reproductive Toxicology,5, 39–44.
Cohort 2 parameters:
Wise (1996), ‚Methods for Assessing Sperm Motility, Morphology, and Counts in the Rat, Rabbit, and Dog: a Consensus Report‘, Reproductive Toxicology, 10, 237–244.
Detailed description of the procedures used to standardise observations and procedures as well as operational definitions for scoring observations;
Russell and S. Schrader (1992), ‚Methods for Assessing Rat Sperm Motility‘, Reproductive Toxicology, 6, 267–273.
List of all test procedures used, and justification for their use;
Suarez (1992), ‚Direct Effects of Ethane Dimethanesulphonate on Epididymal Function in Adult Rats: an In Vitro Demonstration‘, Journal of Andrology, 13, 409–421.
Details of the behavioural/functional, neuropathological and morphometric procedures used, including information and details on automated devices;
Perreault (1991), ‚Rat Sperm Motility Analysis: Methodologic Considerations‘, Reproductive Toxicology, 5, 449–458.
Procedures for calibrating and ensuring the equivalence of devices and the balancing of treatment groups in testing procedures;
Perreault (1993), ‚Computer-Assisted Sperm Analysis of Rodent Epididymal Sperm Motility Using the Hamilton-Thorn Motility Analyzer‘, Methods in Toxicology, Part A, Academic, Orlando, Florida, str. 319–333.
Short justification explaining any decisions involving professional judgment;
Smith (1989), ‚The Automated Analysis of Rat Sperm Motility Following Subchronic Epichlorhydrin Administration: Methodologic and Statistical Considerations‘, Journal of Andrology, 10, 401–415.
Detailed description of all behavioural/functional, neuropathological and morphometric findings by sex and dose group, including both increases and decreases from controls;
Suarez (1992), ‚Endpoints of Spermatoxicity in the Rat After Short Duration Exposures to Fourteen Reproductive Toxicants‘, Reproductive Toxicology, 6, 491–505.
Brain weight;
OECD (2008), Guidance Document on Mammalian Reproductive Toxicity Testing and Assessment, Series on Testing and Assessment, No.
Any diagnoses derived from neurological signs and lesions, including naturally-occurring diseases or conditions;
43, ENV/JM/MONO(2008)16, OECD, Paris.
Images of exemplar findings;
Working, P.K., M. Hurtt (1987), ‚Computerized Videomicrographic Analysis of Rat Sperm Motility‘, Journal of Andrology, 8, 330–337.
Low-power images to assess homology of sections used for morphometry;
Bolin, B., R. Garman, K. Jensen, G. Krinke, B. Stuart, and an ad Hoc Working Group of the STP Scientific and Regulatory Policy Committee (2006), ‚A ‚Best Practices‘ Approach to Neuropathologic Assessment in Developmental Neurotoxicity Testing – for Today‘, Toxicological Pathology, 34, 296–313.
Statistical treatment of results, including statistical models used to analyse the data, and the results, regardless of whether they were significant or not;
Stütz, N., B. Bongiovanni, M. Rassetto, A. Ferri, A.M. Evangelista de Duffard, and R. Duffard (2006), ‚Detection of 2,4-dichlorophenoxyacetic Acid in Rat Milk of Dams Exposed During Lactation and Milk Analysis of their Major Components‘, Food Chemicals Toxicology, 44, 8–16.
Relationship of any other toxic effects to a conclusion about the neurotoxic potential of the test chemical, by sex and dose group;
Forsythe (2007), ‚Variations in Phytoestrogen Content between Different Mill Dates of the Same Diet Produces Significant Differences in the Time of Vaginal Opening in CD-1 Mice and F344 Rats but not in CD Sprague Dawley Rats‘, Environmental health perspectives, 115(12), 1717–1726.
Impact of any toxicokinetic information on the conclusions;
Sobotka (2008), ‚Identification and Interpretation of Developmental Neurotoxicity Effects: a Report from the ILSI Research Foundation/Risk Science Institute Expert Working Group on Neurodevelopmental Endpoints‘, Neurotoxicology and Teratology, 30:
Data supporting the reliability and sensitivity of the test method (i.e.positive and historical control data);
OECD (1996), Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, OECD Guideline for Testing of Chemicals, No.
Relationships, if any, between neuropathological and functional effects;
422, OECD, Paris.
NOAEL or benchmark dose for dams and offspring, by sex and dose group;
Poglavje B.43 te priloge, Študija nevrotoksičnosti na glodalcih.
Discussion of the overall interpretation of the data based on the results, including a conclusion of whether or not the chemical caused developmental neurotoxicity and the NOAEL;
OECD (2000), Guidance Document on the recognition, assessment, and use of clinical signs as humane endpoints for experimental animals used in safety evaluations, Series on Testing and Assessment, No.
Cohort 3 parameters:
19, ENV/JM/MONO(2000)7, OECD, Paris.
Serum IgM antibody titres (sensitisation to SRBC or KLH), or splenic IgM PFC units (sensitisation to SRBC);
Poglavje B.53 te priloge, Študija razvojne nevrotoksičnosti.
Performance of the TDAR method should be confirmed as part of the optimisation process by laboratory setting up the assay for the first time, and periodically (e.g. yearly) by all laboratories;
Poglavje B.54 te priloge, Uterotropni biološki preskus na glodavcih:
Discussion of the overall interpretation of the data based on the results, including a conclusion of whether or not the chemical caused developmental immunotoxicity and the NOAEL;
kratkotrajni presejalni preskus za estrogene lastnosti.
Discussion of results
Poglavje B.55 te priloge, Hershbergerjev biološki preskus na podganah:
Conclusions, including NOAEL values for parental and offspring effects
kratkotrajni presejalni preskus za (anti)androgene lastnosti.
All information not obtained during the study, but useful for the interpretation of the results (e.g. similarities of effects to any known neurotoxicants), should also be provided.
OECD (2009), Guidance Document for Histologic Evalution of Endocrine and Reproductive Test in Rodents, Series on Testing and Assessment, No.
Interpretation of Results
106, OECD, Paris.