natgillin/translations-raw huggingface dataset:
Oviduct, uterus and vagina are examined for appropriate organ-typic development.
Toxiska eller andra effekter på reproduktionen, inklusive antal och procentsatser för djur som parat sig, dräktighet, förlossning och laktation, för haninducerad dräktighet, för honor med tecken på dystoki/långvarig eller svår förlossning.
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).
Dräktighetstid och, om uppgift finns, förlossningens varaktighet.
When possible, sections of the rete testis should be examined.
Antalet implantationer, kullstorlek och procentandelen hanungar.
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.
Antal och procentandel av postimplantationsförlust, levande födda och dödfödda.
Cohort 2 animals
Data om kullvikt och ungvikt (hanar, honor och i kombination), antalet småväxta ungar om det fastställs.
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).
Antal ungar med grava synliga missbildningar.
Brain histopathology is performed for all high-dose and control cohort 2B animals per sex on PND 21 or PND 22.
Toxiska eller andra effekter på avkomman, postnatal tillväxt, levnadsduglighet, etc.
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.
Uppgifter om fysiska markörer hos ungar och andra postnatala utvecklingsdata.
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.
Uppgifter om könsmognad hos F1-djur.
For cohort 2A only, the eyes (retina and optic nerve) and samples of peripheral nerve, muscle and spinal cord are examined.
Uppgifter om funktionsobservationer av ungar och vuxna, i tillämpliga fall.
All neurohistological procedures should be consistent with test method B.53 (35).
Kroppsvikt vid avlivning och absoluta och relativa organviktsdata för P- och vuxna F1-djur.
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.
Obduktionsfynd.
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.
En detaljerad redogörelse av alla histopatologiska fynd.
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).
Totalt spermieantal i cauda epididymis, procentandel progressivt rörliga spermier, procentandel morfologiskt normala spermier, och procentandel av spermier med varje identifierad abnormitet för P- och F1-hanar.
Non-homologous sections should not be used.
Antal och mognadsstadier för de folliklar som finns i äggstockarna hos P- och F1-honor, i förekommande fall.
While the objective is to sample all animals reserved for this purpose (10/sex/dose level), smaller numbers may still be adequate.
Uppräkning av gulkroppar i äggstockarna hos F1-honor.
However, samples from fewer than 6 animals/sex/dose level would generally not be considered sufficient for the purposes of this test method.
Statistisk bearbetning av resultaten, i tillämpliga fall.
Stereology may be used to identify treatment-related effects on parameters such as volume or cell number for specific neuroanatomic regions.
Kohort 2 parametrar:
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.
Detaljerad beskrivning av de förfaranden som används för att standardisera observationer och förfaranden, samt operationella definitioner för att bedöma observationer.
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.
Förteckning över samtliga testförfaranden, samt motivering för deras användning.
Data are reported individually and summarised in tabular form.
Närmare uppgifter om de beteendemässiga/funktionella, neuropatologiska och morfometriska förfaranden som används, inklusive information och detaljer om automatiserade enheter.
Where appropriate, for each test group and each generation, the following should be reported:
Rutiner för kalibrering och säkerställande av likvärdiga enheter och balansen mellan behandlingsgrupperna i testförfarandena.
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.
Kort motivering som förklarar eventuella beslut som inbegriper en yrkesmässig bedömning.
A description of the toxicity, including time of onset, duration, and severity should also be reported.
Detaljerad beskrivning av alla beteendemässiga/funktionella, neuropatologiska och morfometriska resultat från respektive kön och dosgrupp, omfattande både ökningar och minskningar från kontroller.
Numerical results should be evaluated by an appropriate, and accepted statistical method.
Hjärnvikt.
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.
Eventuella diagnoser som härrör från neurologiska symtom och skador, inklusive naturligt förekommande sjukdomar eller tillstånd.
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.
Bilder på typiska exempel på fynd.
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.
Lågupplösta bilder för att bedöma homologi i snitt som används för morfometri.
Evaluation of results
Statistisk bearbetning av resultaten, inklusive statistiska modeller som används för att analysera data, och resultaten, oavsett om de var signifikanta eller ej.
The findings should be evaluated in terms of the observed effects, including necropsy and microscopic findings.
Samband med eventuella toxiska effekter till en slutsats om testkemikaliens neurotoxiska potential, efter kön och dosgrupp.
The evaluation includes the relationship, or lack thereof, between the dose and the presence, incidence, and severity of abnormalities, including gross lesions.
Påverkan av eventuell toxikokinetisk information på slutsatserna.
Target organs, fertility, clinical abnormalities, reproductive and litter performance, body weight changes, mortality and any other toxic and developmental effects should also be assessed.
Data som stöder testmetodens tillförlitlighet och känslighet (dvs. positiva och historiska kontrolldata).
Special attention should be given to sex-specific changes.
Eventuella samband mellan neuropatologiska och funktionella effekter.
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.
Noael eller referensdos för moderdjur och avkomma, för respektive kön och dosgrupp.
The test report should include the following information obtained in the present study from P, F1 animals and F2 animals (where relevant):
Diskussion om den övergripande tolkningen av data baserat på resultaten, inklusive en slutsats om huruvida kemikalien orsakat utvecklingsneurotoxicitet samt Noael.
All relevant available information on the chemical, toxicokinetic and toxicodynamic properties of the test chemical;
Kohort 3 parametrar:
Identification data;
IgM-antikroppstitrar i serum (sensibilisering mot SRBC eller KLH) eller IgM PFC-enheter i mjälte (sensibilisering mot SRBC).
Purity;
TDAR-metodens prestanda bör därför bekräftas som en del av optimeringsprocessen av laboratorier som inför testet för första gången, och med jämna mellanrum (t.ex. årligen) hos alla laboratorier.
Justification for choice of vehicle if other than water;
Diskussion om den övergripande tolkningen av data baserat på resultaten, inklusive en slutsats om huruvida kemikalien orsakat utvecklingsimmunotoxicitet samt Noael.
Species/strain used;
Diskussion av resultaten
Number, age and sex of animals;
Slutsatser, inbegripet Noael-värden för effekter på föräldrar och avkomma
Source, housing conditions, diet, nesting materials, etc.;
All information som inte erhållits under studien men som är användbara för tolkningen av resultaten (t.ex.likheter med effekter från alla kända neurotoxiska ämnen) bör också lämnas.
Individual weights of animals at the start of the test;
Tolkning av resultaten
Vaginal smear data for P females before initiation of treatment (if data are collected at that time);
En utökad engenerationsstudie av reproduktionstoxicitet ger information om verkningarna av upprepad exponering för en kemikalie under alla faser av reproduktionscykeln, vid behov.
P generation pairing records indicating male and female partner of a mating and mating success;
I synnerhet ger studien information om reproduktionssystemet och om utveckling, tillväxt, överlevnad och funktionella endpoints hos avkomma upp till PND 90.
Litter of origin records for adult F1 generation animals;
Tolkning av studiens resultat bör ta hänsyn till all tillgänglig information om kemikalien, inklusive fysikalisk-kemiska, TK och toxikodynamiska egenskaper, tillgängliga relevanta uppgifter om strukturella analoger, samt resultat från toxicitetsstudier som tidigare genomförts med testkemikalien (t.ex.akut toxicitet, toxicitet efter upprepad applikation, mekanistiska studier och studier som bedömer om det finns betydande kvalitativa och kvantitativa artskillnader för metaboliska egenskaper in vivo/in vitro).
Rationale for dose level selection;
Obduktions- och organviktsresultat bör bedömas i samband med observationer gjorda i andra studier med upprepad dosering, när så är möjligt.
Details of test chemical formulation/diet preparation, achieved concentrations;
Minskningar i avkommans tillväxt kan övervägas i relation till en påverkan av testkemikalien på mjölkens sammansättning (se hänvisning 29).
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;
Kohort 2 (utvecklingsneurotoxicitet)
Details of the administration of the test chemical;
Neurobeteendemässiga och neuropatologiska resultat bör tolkas mot bakgrund av samtliga resultat, med hjälp av en metod som bygger på evidensvärde och som involverar expertbedömning.
Conversion from diet/drinking water test chemical concentration (ppm) to the achieved dose (mg/kg body weight/day), if applicable;
Bedömningen av utvecklingsneurotoxicitet, inklusive mänskliga epidemiologiska studier eller fallrapporter, samt experimentella djurstudier (t.ex. toxikokinetiska data, struktur-aktivitetsinformation, data från andra toxicitetsstudier) bör ingå i denna karakterisering.
Details of food and water quality (including diet composition, if available);
För vägledning om tolkningen av utvecklingsmässiga neurotoxiska resultat, se testmetod B.53 (se hänvisning 35) och Tyl et al., 2008 (se hänvisning 31).
Detailed description of the randomisation procedures to select pups for culling and to assign pups to test groups;
Kohort 3 (utvecklingsimmunotoxicitet)
Environmental conditions;
Undertryckning eller förstärkning av immunfunktion bedömd genom TDAR (T-cellsberoende antikroppsrespons) bör utvärderas mot bakgrund av samtliga iakttagelser som gjorts.
List of study personnel, including professional training;
Betydelsen av resultatet från TDAR kan stödjas av andra effekter på immunologiskt relaterade indikatorer (t.ex. benmärgens cellularitet, lymfvävnadens vikt och histopatologi, lymfocytdelmängdsfördelning).
Results (summary and individual data by sex and dose):
Effekter som fastställts genom TDAR kan vara mindre meningsfulla vid annan toxicitet som observerats vid lägre exponering.
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;
OECD:s vägledning 43 bör användas som stöd vid tolkningen av reproduktions- och neurotoxicitetsresultaten (se hänvisning 26).
Absorption data (if available);
Whitby (2006), ’A Tiered Approach to Life Stages Testing for Agricultural Chemical Safety Assessment’, Critical Reviews in Toxicology, 36, 69–98.
Body weight data for P animals;
Moser, V.C., I. Walls och 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.
Body weight data for the selected F1 animals postweaning;
Goodman (1999), ’Stimulating Research to Improve the Scientific Basis of Risk Assessment’, Toxicological Sciences, 49, 1–4.
Time of death during the study or whether animals survived to termination;
Palmer (1995), ’Detection of Effects on Male Reproduction – a Literature Survey’, Journal of the American College of Toxicologists, 14, 293–327.
Nature, severity and duration of clinical observations (whether reversible or not);
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.
Haematology, urinalysis and clinical chemistry data including TSH and T4;
’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.
Phenotypic analysis of spleen cells (T-, B-, NK-cells);
, ’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.
Bone marrow cellularity;
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.
Toxic response data;
Weiner (1977), ’Preputial Separation as an External Sign of Pubertal Development in the Male Rat’, Biological Reproduction, 17, 298–303.
Number of P and F1 females with normal or abnormal oestrous cycle and cycle duration;
, ’Use of SRBC Antibody Responses for Immunotoxicity Testing’, Methods, 41, 9–19.
Time to mating (precoital interval, the number of days between pairing and mating);
Herzyk (2004), ’Primary Antibody Response to Keyhole Limpet Hemocyanin in Rat as a Model for Immunotoxicity Evaluation’, Toxicology, 197, 23–35.
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;
Gray, L.E., J. Ostby, J. Ferrell, G. Rehnberg, R. Linder, R. Cooper, J. Goldman, V. Slott och 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.
Duration of pregnancy and, if available, parturition;
Killian (1978), ’Daily Sperm Production and Epididymal Sperm Reserves of Pubertal and Adult Rats’, Journal of Reproduction and Fertility,54, 103–107.
Numbers of implantations, litter size and percentage of male pups;
Wise (1996), ’Methods for Assessing Sperm Motility, Morphology, and Counts in the Rat, Rabbit, and Dog: a Consensus Report’, Reproductive Toxicology, 10, 237–244.
Number and percent of post-implantation loss, live births and stillbirths;
Russell och S. Schrader (1992), ’Methods for Assessing Rat Sperm Motility’, Reproductive Toxicology, 6, 267–273.
Litter weight and pup weight data (males, females and combined), the number of runts if determined;
Suarez (1992), ’Direct Effects of Ethane Dimethanesulphonate on Epididymal Function in Adult Rats: an In Vitro Demonstration’, Journal of Andrology, 13, 409–421.
Number of pups with grossly visible abnormalities;
Perreault (1991), ’Rat Sperm Motility Analysis: Methodologic Considerations’, Reproductive Toxicology, 5, 449–458.
Toxic or other effects on offspring, postnatal growth, viability, etc.;
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. s. 319–333.
Data on physical landmarks in pups and other postnatal developmental data;
Smith (1989), ’The Automated Analysis of Rat Sperm Motility Following Subchronic Epichlorhydrin Administration: Methodologic and Statistical Considerations’, Journal of Andrology, 10, 401–415.
Data on sexual maturation of F1 animals;
Suarez (1992), ’Endpoints of Spermatoxicity in the Rat After Short Duration Exposures to Fourteen Reproductive Toxicants’, Reproductive Toxicology, 6, 491–505.
Data on functional observations in pups and adults, as applicable;
OECD (2008), Guidance Document on Mammalian Reproductive Toxicity Testing and Assessment, Series on Testing and Assessment, No.
Body weight at sacrifice and absolute and relative organ weight data for the P and adult F1 animals;
43, ENV/JM/MONO(2008)16, OECD, Paris.
Necropsy findings;
Working, P.K., M. Hurtt (1987), ’Computerized Videomicrographic Analysis of Rat Sperm Motility’, Journal of Andrology, 8, 330–337.
Detailed description of all histopathological findings;
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.
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;
Stütz, N., B. Bongiovanni, M. Rassetto, A. Ferri, A.M. Evangelista de Duffard, och 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.
Numbers and maturational stages of follicles contained in the ovaries of P and F1 females, where applicable;
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.
Enumeration of corpora lutea in the ovaries of F1 females;
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:
Statistical treatment of results, where appropriate;
OECD (1996), Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, OECD Guideline for Testing of Chemicals, No.
Cohort 2 parameters:
422, OECD, Paris.
Detailed description of the procedures used to standardise observations and procedures as well as operational definitions for scoring observations;
Kapitel B.43 i denna bilaga, Test avseende neurotoxicitet på gnagare.
List of all test procedures used, and justification for their use;
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.
Details of the behavioural/functional, neuropathological and morphometric procedures used, including information and details on automated devices;
19, ENV/JM/MONO(2000)7, OECD, Paris.
Procedures for calibrating and ensuring the equivalence of devices and the balancing of treatment groups in testing procedures;
Kapitel B.53 i denna bilaga, Studie av utvecklingsneurotoxicitet.
Short justification explaining any decisions involving professional judgment;
Kapitel B.54 i denna bilaga, Uterotrof bioassay på gnagare:
Detailed description of all behavioural/functional, neuropathological and morphometric findings by sex and dose group, including both increases and decreases from controls;
Ett korttidsscreeningtest för östrogena egenskaper.
Brain weight;
Kapitel B.55 i denna bilaga, Hershbergers bioassay på råtta:
Any diagnoses derived from neurological signs and lesions, including naturally-occurring diseases or conditions;
Ett korttidsscreeningtest för (anti-)androgena egenskaper.
Images of exemplar findings;
OECD (2009), Guidance Document for Histologic Evalution of Endocrine and Reproductive Test in Rodents, Series on Testing and Assessment, No.
Low-power images to assess homology of sections used for morphometry;
106, OECD, Paris.
Statistical treatment of results, including statistical models used to analyse the data, and the results, regardless of whether they were significant or not;
OECD (2011), Guidance Document on the Current Implementation of Internal Triggers in the Extended One Generation Reproductive Toxicity Study in the United States and Kanada, Series on Testing and Assessment, No.
Relationship of any other toxic effects to a conclusion about the neurotoxic potential of the test chemical, by sex and dose group;
117, ENV/JM/MONO(2011)21, OECD, Paris.
Impact of any toxicokinetic information on the conclusions;
151, OECD, Paris.
Data supporting the reliability and sensitivity of the test method (i.e.positive and historical control data);
Mått och observationer som ingår i testbatteriet för funktionsobservation (kohort 2A)
Relationships, if any, between neuropathological and functional effects;
Bur & öppet område
NOAEL or benchmark dose for dams and offspring, by sex and dose group;
Manipulation
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;
Fysiologi
Cohort 3 parameters:
Hållning
Serum IgM antibody titres (sensitisation to SRBC or KLH), or splenic IgM PFC units (sensitisation to SRBC);
Enkelt avlägsnande
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;
Temperatur
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;
Ofrivilliga kloniska & toniska rörelser
Discussion of results
Lätthanterlighet
Conclusions, including NOAEL values for parental and offspring effects
Ögonlocksstängning
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.
Muskeltonus
Interpretation of Results
Pupillrespons