natgillin/translations-raw huggingface dataset:
This is necessary because normal divergence in development will result in differential stage distributions within each replicate tank.
Kõikide pidevate kvantitatiivsete näitajate (tagajäseme pikkus, ninamiku-päraku vahemaa, märgkaal) puhul, kus doosi-toime sõltuvus on monotoonne, tuleks kemikaali olulise toime kindlakstegemiseks astmeliselt kohaldada Jonckheere'i-Terpstra testi.
Animals selected for histopathology (n = 5 from each replicate) should be matched to the median stage of the controls (pooled replicates) whenever possible.
Pidevate näitajate puhul, kus doosi-toime sõltuvus ei ole monotoonne, tuleks andmeid hinnata normaaljaotuse seisukohast (soovitatavalt Shapiro-Wilki või Anderson-Darlingi testiga) ja dispersiooni homogeensuse seisukohast (soovitatavalt Levene'i testiga).
If there are replicate tanks with more than five larvae at the appropriate stage, then five larvae are randomly selected.
Mõlemad testid tehakse ANOVA analüüsi jääkidega.
If there are replicate tanks with less than five larvae at the appropriate stage, then randomly selected individuals from the next lower or upper developmental stage should be sampled to reach a total sample size of five larvae per replicate.
Normaaljaotuse ja dispersiooni homogeensuse formaalsete testide asemel võib kasutada ka eksperthinnangut, kuid formaalseid teste tuleb eelistada.
Preferably, the decision to sample additional larvae from either the next lower or upper developmental stage should be made based on an overall evaluation of the stage distribution in the control and chemical treatments.
Kui selgub, et tegemist ei ole normaaljaotusega või dispersioon on heterogeenne, tuleks otsida normaliseeriv, dispersiooni stabiliseeriv teisendus.
That is, if the chemical treatment is associated with a retardation of development, then additional larvae should be sampled from the next lower stage.
Kui andmed (võib-olla pärast teisendust) on normaaljaotusega ja dispersioon on homogeenne, leitakse oluline kemikaaliga kokkupuute mõju Dunnetti testiga.
In turn, if the chemical treatment is associated with an acceleration of development, then additional larvae should be sampled from the next upper stage.
Kui andmed (võib-olla pärast teisendust) on normaaljaotusega, kuid dispersioon on heterogeenne, leitakse oluline kemikaaliga kokkupuute mõju Tamhane'i-Dunnetti või T3-testiga või Mann-Whitney-Wilcoxoni U-testiga.
In cases of severe alterations of tadpole development due to treatment with a test chemical, there might be no overlap of the stage distribution in the chemical treatments with the calculated control median developmental stage.
Kui ei õnnestu leida normaliseerivat teisendust, leitakse oluline kemikaaliga kokkupuute mõju Mann-Whitney-Wilcoxoni U-testiga, kasutades p-väärtuste kohandamist Bonferroni-Holmi järgi.
In only these cases, the selection process should be modified by using a stage different from the control median stage to achieve a stage-matched sampling of larvae for thyroid histopathology.
Dunnetti testi kasutatakse sõltumatult ANOVA F-testist ja Mann-Whitney testi kasutatakse sõltumatult Kruskall-Wallise testist.
Furthermore, if stages are indeterminate (i.e., asynchrony), then 5 tadpoles from each replicate should be randomly chosen for histological analysis.
Olulist suremust ei eeldata, kuid seda tuleks hinnata astmelise Cochran-Armitage'i testiga, kui andmed on kooskõlas doosi-toime vahelise monotoonse sõltuvusega; vastupidisel juhul tuleks teha Fisheri täpne test Bonferroni-Holmi kohandusega.
The rationale underlying sampling of any larvae that are not at a stage equivalent to the control median developmental stage should be reported.
Seda, kas kemikaaliga kokkupuude avaldab olulist mõju arengustaadiumile, kontrollitakse Jonckheere'i-Terpstra testi astmelise rakendamisega paralleelkatsete mediaanidele.
Determination of Biological Endpoints
Teise võimalusena ja eelistatavalt tuleks mõju kindlakstegemiseks kasutada multikvantaalset Jonckheere'i testi 20. kuni 80. protsentiilini, kuna selles võetakse arvesse jaotusprofiili muutusi.
During the 21 day exposure phase, measurement of primary endpoints is performed on days 7 and 21, however daily observation of test animals is necessary.
Sobiv analüüsiüksus on paralleelkatse, nii et andmed kujutavad endast paralleelkatsete mediaane, kui kasutatakse Jonckheere'i-Terpstra või Mann-Whitney U-testi või paralleelkatsete keskväärtusi, kui kasutatakse Dunnetti testi.
Table 3 provides an overview of the measurement endpoints and the corresponding observation time points.
Doosi-toime monotoonsust võib hinnata visuaalselt kokkupuute- ja paralleelrühmade keskväärtuste või mediaanide põhjal või formaalsete testidega, nagu on kirjeldatud eespool (11).
More detailed information for technical procedures for measurement of apical endpoints and histological assessments is available in the OECD guidance documents (9).
Vähem kui viie paralleelkatse puhul ühe kokkupuutetaseme või kontrolli kohta tuleks kasutada Jonckheere'i-Terpstra ja Mann-Whitney testide täpse permutatsiooni versioone, kui need on kättesaadavad.
Observation time points for primary endpoints in the AMA
Kõikide osutatud testide statistilist olulisust hinnatakse olulisusnivoo 0,05 juures.
Apical Endpoints
Joonisel 4 on esitatud pideva toime andmete statistiliste testide tegemise otsustamisskeem.
Daily
Pidevale toimele osutavate andmete statistiliste töötluste otsustamisskeem.
Mortality
Konkreetsed kaalutlused andmete analüüsi puhul
Hind Limb Length
Ebaõnnestunud kokkupuutetasemekatsete kasutamine
Snout-Vent Length
Kui otsustatakse, et kas ühe paralleelkatse või terve kokkupuutetaseme puhul võib avalduda selge mürgisus ja see tuleks analüüsist kõrvale jätta, tuleb arvestada mitut tegurit.
Wet Body Weight
Selge mürgisus on määratletud rohkem kui kahe surmajuhtumiga ühes paralleelkatses, mida saab panna üksnes mürgisuse arvele ja mis ei saa olla tingitud tehnilisest veast.
Thyroid Gland Histology
Muud selge mürgisuse nähud on järgmised: veritsemine, ebatavaline käitumine, ebatavaline ujumisviis, isutus ja muud kliinilised haigustunnused.
Developmental stage, hind limb length, SVL and wet weight are the apical endpoints of the AMA, and each is briefly discussed below.
Subletaalse mürgisuse puhul võib olla vajalik kvalitatiivne hindamine; selle tegemisel peaks alati olema aluseks võrdlemine puhta vee kontrollrühmaga.
Further technical information for collecting these data is available in the guidance documents referenced including procedures for computer-assisted analysis which are recommended for use.
Lahusti kontrollkatsed
The developmental stage of X. laevis tadpoles is determined using the staging criteria of Nieuwkoop and Faber (8).
Lahusti kasutamist tuleks kaaluda ainult viimase abinõuna, kui kõik muud kemikaali lisamise võimalused on läbi vaadatud.
Developmental stage data are used to determine if development is accelerated, asynchronous, delayed or unaffected.
Kui kasutatakse lahustit, tuleb samal ajal teha kontrollkatse puhta veega.
Acceleration or delay of development is determined by making a comparison between the median stage achieved by the control and treated groups.
Katse lõpetamisel tuleb hinnata lahusti võimalikku mõju.
Asynchronous development is reported when the tissues examined are not malformed or abnormal, but the relative timing of the morphogenesis or development of different tissues is disrupted within a single tadpole.
Seda tehakse lahusti kontrollrühma ja puhta vee kontrollrühma statistilise võrdlemisega.
Differentiation and growth of the hind limbs are under control of thyroid hormones and are major developmental landmarks already used in the determination of developmental stage.
Kõige asjakohasemad näitajad, mida tuleks sellise analüüsi juures arvesse võtta, on arengustaadium, ninamiku-päraku vahekaugus ja märgkaal, kuna neid võib mõjutada muu kui kilpnäärmega seotud mürgisus.
Hind limb development is used qualitatively in the determination of developmental stage, but is considered here as a quantitative endpoint.
Kui nende näitajate vahel tuvastatakse statistiliselt olulisi erinevusi vee kontrollrühma ja lahusti kontrollrühma vahel, määratakse uuringu eesmärgiks olevad näitajad mõõdetud toime võrdlusest puhta vee kontrollrühmaga.
Therefore, hind limb length is measured as an endpoint to detect effects on the thyroid axis (Figure 2).
Kui mõõdetud muutujate puhul puudub statistiliselt oluline erinevus puhta vee kontrollrühma ja lahusti kontrollrühma vahel, määratakse uuringu eesmärgiks olevad näitajad mõõdetud toime võrdlusest lahjendusvee ja lahusti kontrollrühmade ühendatud tulemustega.
For consistency, hind limb length is measured on the left hind limb.
Kokkupuude kemikaaliga rühmade puhul, kes jõuavad 60. või kõrgema arengustaadiumini
Hind limb length is evaluated both at day 7 and at day 21 of the test.
Üks lähenemisviis on võtta märgkaalu ja ninamiku-päraku vahemaa statistilistes analüüsides arvesse vaid kulleseid arengustaadiumiga kuni 60.
On day 7, measuring hind limb length is straightforward, as illustrated in Figure 2.
Arvatakse, et see lähenemisviis annab piisavalt usaldusväärseid andmeid võimaliku mõju kohta kasvule, kui analüüsidest jäetakse välja üksnes väike osa (≤ 20 %) katseloomadest.
However, measuring hind limb length on day 21 is more complicated due to bends in the limb.
Kui rohkem kulleseid (≥20 %) on ühel või mitmel nimikontsentratsioonil jõudnud arengus 60. staadiumist kaugemale, tuleks kõikide kulleste puhul kasutada kahefaktorilist ANOVAd, millesse on pesastatud dispersioonistruktuur, et hinnata kemikaaliga kokkupuutest tingitud mõju kasvule, võttes arvesse hiliste arengustaadiumide mõju kasvule.
Therefore, measurements of hind limb length at day 21 should originate at the body wall and follow the midline of the limb through any angular deviations.
liites on esitatud suunised massi ja pikkuse andmete kahefaktorilise ANOVA analüüsi tegemiseks.
Changes in hind limb length at day 7, even if not evident at day 21, are still considered significant for potential thyroid activity.
Series on Testing and Assessment.
Length measurements are acquired from digital photographs using image analysis software as described in the OECD Guidance Document on Amphibian Thyroid Histology (9).
No.
Body Length and Wet Weight
77, Paris.
Determinations of snout to vent length (SVL) (Figure 2) and wet weight are included in the test protocol to assess possible effects of test chemicals on the growth rate of tadpoles in comparison to the control group and are useful in detecting generalised toxicity to the test chemical.
Physiology of Amphibia.
Because the removal of adherent water for weight determinations can cause stressful conditions for tadpoles and may cause skin damage, these measurements are performed on the day 7 sub-sampled tadpoles and all remaining tadpoles at test termination (day 21).
Lofts,B.
For consistency, use the cranial aspect of the vent as the caudal limit of the measurement.
(ed.), Academic Press, New York, pp.
Snout to vent length (SVL) is used to assess tadpole growth as illustrated in Figure 2.
467-599
Types of body length measurements and (B) Hind limb length measurements for X. laevis tadpoles (1)
Kahepaiksete metamorfoosi 21-päevase katse tingimused
While developmental stage and hind limb length are important endpoints to evaluate exposure-related changes in metamorphic development, developmental delay cannot, by itself, be considered a diagnostic indicator of anti-thyroidal activity.
Katseloomad
Some changes may only be observable by routine histopathological analysis.
Xenopus laevis'e vastsed (kullesed)
Diagnostic criteria include thyroid gland hypertrophy/atrophy, follicular cell hypertrophy, follicular cell hyperplasia, and as additional qualitative criteria:
Vastsete arengustaadium katse alguses
follicular lumen area, colloid quality and follicular cell height/shape.
arengustaadium Nieuwkoopi ja Faberi järgi
Severity grading (4 grades) should be reported.
Kokkupuuteaeg
Information on obtaining and processing samples for histological analysis and for performing histologic analyses on tissue samples is available in “Amphibian Metamorphosis Assay: Part 1 — Technical guidance for morphologic sampling and histological preparation” and “Amphibian Metamorphosis Assay: Part 2 — Approach to reading studies, diagnostic criteria, severity grading and atlas” (9).
21 päeva
Laboratories performing the assay for the first time(s) should seek advice from experienced pathologists for training purpose prior to undertaking histological analysis and evaluation of the thyroid gland.
Kulleste valiku kriteeriumid
Overt and significant changes in apical endpoints indicating developmental acceleration or asynchrony may preclude the necessity to perform histopathological analysis of the thyroid glands.
Arengustaadium ja kogupikkus (valikuline)
However, absence of overt morphological changes or evidence of developmental delay warrants histological analyses.
Katses kasutatavad kontsentratsioonid
All test tanks should be checked daily for dead tadpoles and the numbers recorded for each tank.
Vähemalt 3 kontsentratsiooni ligikaudu ühe suurusjärgu vahemikus
The date, concentration and tank number for any observation of mortality should be recorded.
Kokkupuuterežiim
Dead animals should be removed from the test tank as soon as observed.
Läbivooluga (eelistatud) ja/või staatiline uuendussüsteem
Mortality rates exceeding 10 % may indicate inappropriate test conditions or toxic effects of the test chemical.
Voolukiirus katsesüsteemis
Additional Observations
25 ml/min (täielik koguse asendamine ligikaudu iga 2,7 tunni jooksul)
Cases of abnormal behaviour and grossly visible malformations and lesions should be recorded.
Peamised määratavad näitajad / määramise päev
The date, concentration and tank number for any observation of abnormal behaviour, gross malformations or lesions should be recorded.
ja 21. päev
Normal behaviour is characterised by the tadpoles being suspended in the water column with tail elevated above the head, regular rhythmic tail fin beating, periodic surfacing, operculating, and being responsive to stimulus.
Kilpnäärme histoloogia
Abnormal behaviour would include, for example, floating on the surface, lying on the bottom of the tank, inverted or irregular swimming, lack of surfacing activity, and being nonresponsive to stimulus.
Lahjendamiseks kasutatav vesi / laboratoorne kontroll
In addition, gross differences in food consumption between treatments should be recorded.
Aktiivsöel filtrimisega kloorist puhastatud kraanivesi või muu samaväärne laboris kasutatav vesi
Gross malformations and lesions could include morphological abnormalities (e.g. limb deformities), hemorrhagic lesions, bacterial or fungal infections, to name a few.
Kulleste tihedus
These determinations are qualitative and should be considered akin to clinical signs of disease/stress and made in comparison to control animals.
20 kullest katsenõus (5 kullest liitri kohta)
If the occurrence or rate of occurrence is greater in exposed tanks than in the controls, then these should be considered as evidence for overt toxicity.
Uuritav lahus / katsenõu
Data Collection
4–10 l nõu (veekiht vähemalt 10–15 cm) / klaasist või roostevabast terasest nõu (nt 22,5 cm × 14 cm × 16,5 cm)
All data should be collected using electronic or manual systems which conform to good laboratory practices (GLP).
Paralleelkatsed
Characterisation of the test chemical:
4 paralleelkatsetega katsenõu uuritava kontsentratsiooni ja kontrolli kohta
physical-chemical properties;
Lubatav suremuse määr kontrollrühmades
information on stability and biodegradability;
≤ 10 % igas paralleelkatsenõus
Chemical information and data:
Kilpnäärme fikseerimine
method and frequency of preparation of dilutions.
Fikseeritavate kilpnäärmete arv
Test chemical information includes actual and nominal concentrations of the test chemical, and in some cases, non-parent chemical, as appropriate.
Kõik kullesed (algselt hinnatakse 5 kullest paralleelkatse kohta)
Test chemical measurements may be required for stock solutions as well as for test solutions;
Piirkond
Solvent (if other than water):
Pea või kogu keha
justification of the choice of solvent, and characterisation of solvent (nature, concentration used);
Fikseerimisvedelik
Operational records:
Davidsoni fikseerimislahus
these consist of observations pertaining to the functioning of the test system and the supporting environment and infrastructure.
Sööt
Typical records include:
Sera Micron® või samaväärne
ambient temperature, test temperature, photoperiod, status of critical components of the exposure system (e.g. pumps, cycle counters, pressures), flow rates, water levels, stock bottle changes, and feeding records.
Kogus / sagedus
General water quality parameters include:
Vt tabel 1, kui kasutatakse sööta Sera Micron®
pH, DO, conductivity, total iodine, alkalinity, and hardness;
Valgustus
Deviations from the test method:
Valgustusperiood
this information should include any information or narrative descriptions of deviations from the test method;
12 tundi valgust – 12 tundi pimedust
Biological observations and data:
600 kuni 2000 luksi (mõõdetuna vee pinnal)
these include daily observations of mortality, food consumption, abnormal swimming behaviour, lethargy, loss of equilibrium, malformations, lesions, etc.
Vee temperatuur
Observations and data collected at predetermined intervals include:
6,5–8,5
developmental stage, hind limb length, snout vent length, and wet weight;
Lahustunud hapniku sisaldus (DO)
Statistical analytical techniques and justification of techniques used;
> 3,5 mg/l (> 40 % õhu küllastuskontsentratsioonist)
results of the statistical analysis preferably in tabular form;
Analüütilise keemia proovide võtmise ajakava
Histological data:
Üks kord nädalas (4 proovivõtmist katse kohta)
these include narrative descriptions, as well as graded severity and incidence scores of specific observations, as detailed in the histopathology guidance document;
Tabelid lähteandmete ja koondandmete esitamiseks
Ad hoc observations:
Üldine teave uuritava kemikaali kohta
these observations should include narrative descriptions of the study that do not fit into the previously described categories.
Keemilised andmed
Data reporting
Sisestage uuritav kemikaal, kontsentratsiooni ühikud ja kokkupuutekontsentratsioonid
Appendix 2 contains daily data collection spreadsheets that can be used as guidance for raw data entry and for calculations of summary statistics.
Kontsentratsiooni ühik:
Additionally, reporting tables are provided that are convenient for communicating summaries of endpoint data.
Kokkupuutekontsentratsioon 1
Reporting tables for histological assessments can be found in Appendix 2.
Kokkupuutekontsentratsioon 2
Performance Criteria and Test Acceptability/Validity
Kokkupuutekontsentratsioon 3
Generally, gross deviations from the test method will result in unacceptable data for interpretation or reporting.
Kokkupuutekontsentratsioon 4
Therefore, the following criteria in Table 4 have been developed as guidance for determining the quality of the test performed, the general performance of the control organisms.
Kuupäev (0-päev):
Table 4
Märkida kuupäev (pp/kk/aa)
Performance criteria for the AMA
Kuupäev (7. päev):
Criterion
Kuupäev (21. päev):
Acceptable limits
Tabelid lähteandmete kogumiseks 7. ja 21. päeval
Test concentrations
PÄEV X
Maintained at ≤ 20 % CV (variability of measured test concentration) over the 21 day test
KUUPÄEV 00/00/00
Mortality in controls
Kokkupuuterühma number
≤ 10 % — mortality in any one replicate in the controls should not exceed 2 tadpoles
Paralleelkatse number
Minimum median developmental stage of controls at end of test
Isendi number
Spread of development stage in control group
Isendi tunnus
The 10th and the 90th percentile of the development stage distribution should not differ by more than 4 stages
Ninamiku-pärakuava vahemaa (mm)
Dissolved Oxygen
Tagajäseme pikkus (mm)
≥ 40 % air saturation [8]
Kogu organismi märgmass (mg)
pH should be maintained between 6,5-8,5.
Uuritavate näitajate 7. ja 21. päeva andmetest arvutatud koondtulemused
The inter-replicate/inter-treatment differentials should not exceed 0,5.
arvutused lahtrites on seotud tabelisse 2 sisestatud andmetega.
± 1 °C — the inter-replicate/inter-treatment differentials should not exceed 0,5 °C
Mass (mg)
Test concentrations without overt toxicity
Konts.
Replicate performance
Parall.
≤ 2 replicates across the test can be compromised
Mediaan
Special conditions for use of a solvent
Keskmine
If a carrier solvent is used, both a solvent control and clean water control should be used and results reported
Std-hälve
See below for more information
arvutused lahtrites on seotud tabelisse 1 sisestatud andmetega.
Special conditions for static renewal system
Katsepäev
Representative chemical analyses before and after renewal should be reported
Arv paralleelkatses
Ammonia levels should be measured immediately prior to renewal
Arv kokkupuutetaseme kohta
All water quality parameters listed in Table 1of Appendix 1 should be measured immediately prior to renewal
Tabel 5.
Renewal period should not exceed 72 hours
Vee kvaliteedi kriteeriumid
Appropriate feeding schedule (50 % of the daily food ration of commercial tadpole feed)
Kokkupuutesüsteem (läbivooluga / staatiline uuendatav):
Test Validity
Valguse intensiivsus:
The following requirements should be met to deem a test acceptable/valid:
Valguse-pimeduse tsükkel:
Valid experiment in a test determined to be negative for thyroid activity:
Sööt:
For any given treatment (including controls), mortality cannot exceed 10 %.
Söötmismäär:
For any given replicate, mortality cannot exceed three tadpoles, otherwise the replicate is considered compromised
Vee pH
At least two treatment levels, with all four uncompromised replicates, should be available for analysis
Joodi kontsentratsioon katsevees:
At least two treatment levels without overt toxicity should be available for analysis
Tabel 6.
Valid experiment in a test determined to be positive for thyroid activity:
Keemiaandmete koondtabel
Mortality of no more than two tadpoles/replicate in the control group can occur
Kemikaali nimetus:
Decision logic for the conduct of the AMA
CASi nr:
Decision logic was developed for the AMA to provide logical assistance in the conduct and interpretation of the results of the bioassay (see flow chart in Figure 3).
Tabel 7.
The decision logic, in essence, weighs the endpoints in that advanced development, asynchronous development and thyroid histopathology are weighed heavily, while delayed development, snout-vent length and wet body weight, parameters that can potentially be affected by general toxicity, are weighed less heavily.
Tabel histopatoloogiliste leidude esitamiseks põhikriteeriumide järgi
Advanced development (determined using developmental stage, SVL and HLL)
Kuupäev:
Advanced development is only known to occur through effects which are thyroid hormone related.
Keemiline aine:
These may be peripheral tissue effects such as direct interaction with the thyroid hormone receptor (such as with T4) or effects which alter circulating thyroid hormone levels.
Patoloog:
In either case, this is considered sufficient evidence to indicate that the chemical has thyroid activity.
Kilpnäärme hüpertroofia
Advanced development is evaluated in one of two ways.
Kilpnäärme atroofia
First, the general developmental stage can be evaluated using the standardised approach detailed in Nieuwkoop and Faber (8).
Follikulaarrakkude hüpertroofia
Second, specific morphological features may be quantified, such as hind limb length, at both days 7 and 21, which is positively associated with agonistic effects on the thyroid hormone receptor.
Follikulaarrakkude hüperplaasia
If statistically significant advances in development or hind limb length occur, then the test indicates that the chemical is thyroid active.
Kontroll-looma ID – paralleelkatse 1
The evaluation of test animals for the presence of accelerated development relative to the control population will be based on results of statistical analyses performed for the following four endpoints:
Doosilooma ID – paralleelkatse 1
hind limb length (normalised by SVL) on study day 7
Kontroll-looma ID – paralleelkatse 2
hind limb length (normalised by SVL) on study day 21
Doosilooma ID – paralleelkatse 2
developmental stage on study day 7
Kokku: