natgillin/translations-raw huggingface dataset:
The size effect that can be detected with 75-80 % power should be provided for each endpoint with the statistical test to be used.
Regulativni organi lahko zahtevajo izvedbo histopatologije spolnih žlez, da se prouči ciljni organ na osi HPG po izpostavljenosti kemikaliji.
The databases available at the time of development of this test method establish the power possible under the recommended statistical procedures.
Zato se spolne žleze fiksirajo cele ali secirane.
An individual lab should demonstrate its ability to meet this power requirement either by conducting its own power analysis or by demonstrating that the Coefficient of Variation (CV) for each response does not exceed the 90th percentile of CVs used in developing the TG.
Kadar je potrebna histopatologija, se pri oceni endokrinega delovanja preskusne kemikalije iščejo posebni odzivi na spolnih žlezah, povezani z endokrinim sistemom.
Table 1 provides these CVs.
Ti diagnostični odzivi vključujejo predvsem prisotnost oocitov na modih, hiperplazijo Leydigovih celic, slabše tvorjenje rumenjaka, povečanje spermatogonijev in perifolikularno hiperplazijo.
Species
Ocena odzivov biomarkerja z analizo variance
Response
Za opredelitev možnega endokrinega delovanja kemikalije se z analizo variance primerjajo odzivi med tretiranimi in kontrolnimi skupinami.
Rainbow Trout
Vse podatke o biološkem odzivu je treba analizirati in vključiti v poročilo za vsak spol posebej.
Fathead Minnow
Če niso izpolnjene zahtevane domneve za parametrske metode – nenormalna porazdelitev (npr. Shapiro-Wilkov test) ali heterogena varianca (Bartlettov ali Levenejev test), je potreben razmislek o preoblikovanju podatkov, da se poenotijo variance pred izvedbo analize variance ali pred izvedbo tehtane analize variance.
For almost all statistical tests used to evaluate laboratory toxicology studies, the comparisons of interest are of treatment groups to control.
Za nemonoton odziv na odmerek se lahko uporabi Dunnettov test (parametrski) večkratnih primerjav med pari ali Mann-Whitneyjev test z Bonferronijevo prilagoditvijo (neparametrski).
For that reason, it is not appropriate to require a significant ANOVA F-test before using Dunnett's or Williams' test or a significant Kruskal-Wallis test before using the Jonckheere-Terpstra, Mann-Whitney, or Dunn test (Hochberg and Tamhane 1987, Hsu 1996, Dunnett 1955, 1964, Williams 1971, 1972, 1975, 1977, Robertson et al.
Če je odziv na odmerek približno monoton, se lahko uporabijo drugi statistični testi (npr. test po Jonckheere-Terpstraju ali Williamsov test).
1988, Jonckheere 1954, Dunn 1964).
Za lažjo izbiro najprimernejšega statističnega testa je v Dodatku 8 zagotovljen diagram poteka za statistično analizo.
Dunnett's test has a built-in multiplicity adjustment and its false positive and false negative rates are adversely affected by using the F-test as a gatekeeper.
Dodatne informacije so na voljo tudi v dokumentu OECD z naslovom „Sodobni pristopi pri statistični analizi podatkov o ekotoksičnosti: smernice za uporabo“ (ang.
Similarly, the step-down Williams and Jonckheere-Terpstra tests using a 0,05 significance level at every step preserve an overall 5 % false positive rate and that rate and the power of the tests are adversely affected by using the F- or Kruskal-Wallis test as a gatekeeper.
Document on Current Approaches to Statistical Analysis of Ecotoxicity Data) (28).
Mann-Whitney and Dunn's test have to be adjusted for multiplicity and the Bonferroni-Holm adjustment is advised.
Poročanje o rezultatih preskusa
A thorough discussion of most of the recommendations on hypothesis testing and verification of assumptions underlying these tests is given in OECD (2006), which also contains an extensive bibliography.
Podatki študije morajo vključevati naslednje:
Treatment of Controls when a Solvent is Used
Preskusni laboratorij:
If a solvent is used, then both a dilution water control and a solvent control should be included.
odgovorno osebje in njihove obveznosti v zvezi s študijo;
The two controls should be compared for each response and combined for statistical analysis if no significant difference is found between the controls.
vsak laboratorij mora dokazati usposobljenost s sklopom reprezentativnih kemikalij.
Otherwise, the solvent control should be used for NOEC determination or ECx estimation and the water control is not used.
opredelitev lastnosti preskusne kemikalije;
See restriction in the validity criteria (Paragraph 7)
fizikalno stanje in ustrezne fizikalno-kemijske lastnosti;
For length, weight, proportion of egg hatch or larval mortality or abnormal larvae, and first or last day of hatch or swim-up, a T-test or Mann-Whitney test should be used to compare the dilution water- control and the solvent control at the 0,05 significance level, ignoring all treatment groups.
metoda in pogostost priprave preskusnih koncentracij;
The results of these tests should be reported.
informacije o stabilnosti in biološki razgradljivosti.
Size Measurements (length and weight)
opredelitev lastnosti topila (vrsta, uporabljena koncentracija);
Individual fish length and weight values can be normally or log-normally distributed.
utemeljitev izbire topila (če to ni voda).
In either case, the replicate mean values tend to be normally distributed by virtue of the Central Limit Theorem and confirmed from data from well over 100 ELS studies of three freshwater species.
vrsta in sev;
Alternatively, where the data or historical databases suggest a log-normal distribution for individual fish size values, the replicate mean logarithm of the individual fish values can be calculated and the data for analysis can then be the anti-logs of these replicate mean logarithms.
dobavitelj in specifični objekt dobavitelja;
Data should be evaluated for consistency with a normal distribution and variance homogeneity.
starost rib na začetku preskusa in razmnoževalno stanje/stanje drstenja;
For this purpose, the residuals from an ANOVA model with concentration as the single explanatory class variable should be used.
podrobnosti o postopku aklimatizacije živali;
Visual determination from scatterplots and histograms or stem-and-leaf plots can be used.
telesna teža rib na začetku izpostavljenosti (iz podvzorca staleža rib).
Alternatively, a formal test such as the Shapiro-Wilk or Anderson-Darling can be used.
uporabljeni preskusni postopek (vrsta preskusa, stopnja obremenitve, gostota rib itd.);
Consistency with variance homogeneity can be assessed from a visual examination of the same scatter plot or formally from Levene's test.
metoda priprave osnovnih raztopin in pretok;
Only parametric tests (e.g. Williams, Dunnett) need be evaluated for normality or variance homogeneity.
nominalne preskusne koncentracije, tedensko izmerjene koncentracije preskusnih raztopin in uporabljena analitska metoda, sredine izmerjenih vrednosti in standardnih odklonov v preskusnih posodah ter dokazi, da se meritve nanašajo na koncentracije preskusne kemikalije v dejanski raztopini;
Attention should be paid to possible outliers and their effect on analysis.
značilnosti vode za redčenje (vključno s pH, trdoto, alkalnostjo, temperaturo, koncentracijo raztopljenega kisika, ravnmi preostalega klora, skupnim organskim ogljikom, suspendiranimi trdnimi snovmi in drugimi izvedenimi meritvami);
Tukey's outlier test and visual inspection of the same plots of residuals described above can be used.
kakovost vode v preskusnih posodah: pH, trdota, temperatura in koncentracija raztopljenega kisika;
It should be recalled that observations are entire replicates, so omitting an outlier from analysis should be done only after careful consideration.
podrobne informacije o hranjenju (npr. vrsta hrane, vir, dana količina in pogostost dajanja ter analiza zadevnih onesnaževal, če je na voljo (npr. PCB, PAH in organoklorni pesticidi)).
NOEC Flow-Chart Size Measurements (length and weight)
Znake bolezni in znake toksičnih učinkov je treba temeljito oceniti in o njih poročati.
Variances stabilising transform?
Možno je na primer, da na nastajanje VTG pri samicah vplivajo tudi splošna toksičnost in neendokrini toksični načini delovanja, npr. hepatotoksičnost.
Step-down Williams or Jonckherre
Visoke vrednosti VTG pri kontrolnih samcih bi lahko ogrozile odzivnost preskusa in njegovo zmožnost zaznavanja šibkih agonistov estrogena.
Rep means normal, homogenous?
Nizke vrednosti VTG pri kontrolnih samicah bi lahko ogrozile odzivnost preskusa ter njegovo zmožnost zaznavanja zaviralcev aromataze in antagonistov estrogena.
Yes
Pri pripravi zadevnih smernic so bile uporabljene validacijske študije.
Dunn or Mann-Whitney test
V praksi se spodbuja, naj vsak laboratorij vzpostavi lastne podatke o kontrolah iz preteklih preskusov za samce in samice ter pozitivno kontrolo za estrogeno delovanje (npr. 17β-estradiol pri 100 ng/l ali znan šibek agonist), ki povzroči povečanje VTG pri ribjih samcih, pozitivno kontrolo za zaviranje aromataze (npr. fadrozol ali prokloraz pri 300 μg/l), ki povzroči zmanjšanje VTG pri ribjih samicah, in pozitivno kontrolo za androgeno delovanje (npr. 17β-trenbolon pri 5 μg/l), ki povzroči indukcijo sekundarnih spolnih značilnosti pri samicah črnoglavega pisanca in medake.
Dashed figures are paths for 1st and last day of hatch or swimup (*) or abnormal larvae
Vsi ti podatki se lahko primerjajo z razpoložljivimi podatki iz validacijskih študij (1) (2) (3), da se zagotovi usposobljenost laboratorija.
These responses never satisfy assumptions for parametric analysis or models.
Na splošno je treba meritve VTG šteti za pozitivne, če je pri samcih prišlo do statistično značilnega povečanja (p < 0,05) ali pri samicah do statistično značilnega zmanjšanja (p < 0,05) vsaj pri največjem preskušenem odmerku v primerjavi s kontrolno skupino ter ob odsotnosti znakov splošne toksičnosti.
Unless the data are not consistent with the requirements for these tests, the NOEC is determined by a step-down application of Williams' or the Jonckheere-Terpstra test.
Pozitiven rezultat je nadalje podprt s prikazom biološko verjetnega razmerja med odmerkom in krivuljo odziva.
OECD (2006) provides details on these procedures.
Kot je bilo navedeno, zmanjšanje VTG morda ni v celoti endokrinega izvora; vendar je treba pozitiven rezultat na splošno razlagati kot dokaz endokrinega delovanja in vivo ter si prizadevati za nadaljnjo pojasnitev.
For data not consistent with the requirements for a step-down trend test, Dunnett's test or the Tamhane-Dunnett (T3) test can be used, both of which have built-in adjustments for multiplicity.
Regulativni organi lahko zahtevajo oceno histopatologije spolnih žlez, da se določi, ali so preskusne živali sposobne za razmnoževanje, in da se omogoči ocena zanesljivosti dokazov pri rezultatih preskusov.
These tests assume normality and, in the case of Dunnett, variance homogeneity.
Izvedba histopatologije spolnih žlez morda ne bo potrebna, kadar so VTG ali sekundarne spolne značilnosti pozitivne (tj. povečanje ali zmanjšanje VTG ali indukcija sekundarnih spolnih značilnosti).
Where those conditions are not satisfied, Dunn's non-parametric test can be used.
OECD (2006b).
OECD (2006) contains details for all of these tests.
OECD (2007).
Figure 2 is giving an overview, how to find the test of choice.
Owens, J. W.
Egg Hatch and Larval Survival
US EPA (2007).
The data are proportions of eggs that hatch or larvae that survive in individual replicates.
OECD (2008).
These proportions should be assessed for extra-binomial variance, which is common but not universal for such measurements.
Sumpter, J. P. in S. Jobling (1995).
The flowchart in figure 3 is guidance for the test of choice; see text for detailed descriptions.
Pawlowski, S. et al.
Two tests are commonly used.
Andersen, L. et al.
These are Tarone's C(α) test (Tarone, 1979) and chi-squared tests, each applied separately to every test concentration.
Ankley, G. T. et al.
If extra-binomial variance is found in even one test concentration, then methods that accommodate that should be used.
Panter, G. H. et al.
Formula 1
Parks, L. G. et al.
Tarone's C (α) test (Tarone 1979)
Part C Pharmacology, toxicology and endocrinology, 123(2): 113–25.
Where ̂ is the mean proportion for a given concentration, m is the number of replicate tanks, nj is the number of subjects in replicate j, and xj is the number of subjects in that replicate responding, e.g. not hatched or dead.
Fenske, M. et al.
This test is applied to each concentration separately.
C 129 (3): 217–232.
This test can be seen as an adjusted chi-squared test, but limited power simulations done by Tarone have shown it to be more powerful than a chi-squared test.
Holbech, H. et al.
Figure 3
Vitellogenin induction by 17b-estradiol and 17a-ethinylestradiol in male zebrafish (Danio rerio).
NOEC Flow Chart for Egg Hatch and Larval Mortality Yes Yes Yes No
C 131: 531–539.
Are data (*) consistent with a monotone concentration-response?
Brion, F. et al.
Step-down Rao-Scott Cochran-Armitage or Jonckheere test or, after arc-sin square-root transform, Williams test
Development and validation of an enzyme-linked immunosorbent assay to measure vitellogenin in the zebrafish (Danio rerio).
Step-down Cochran-Armitage or Jonckheere test or, after arc-sin square-root transform, Williams test
Environmental Toxicology and Chemistry, zv.
Dunnett test Dunn test or Mann-Whitney No
21: 1699–1708.
Data normally distributed, homogenous after arc-sin square-root transform?
Yokota, H. et al.
C(α) or chi-squared Test for extra-binominal Variance significant?
Journal of Health Science 50: 301–308.
Data are replicate proportion.
Environmental Toxicology and Chemistry, 22(6): 1350–60.
Where there is no significant evidence of extra-binomial variance, the step-down Cochran-Armitage test can be used.
OECD (2010).
This test ignores replicates, so where there is such evidence, the Rao-Scott adjustment to the Cochran-Armitage test (RSCA) takes replicates, replicate sizes, and extra-binomial variance into account and is recommended.
OECD Environmental Health and Safety Publications Series on Testing and Assessment, št. 123, Pariz.
Alternative tests include the step-down Williams and Jonckheere-Terpstra tests and Dunnett's test as described for size measurements.
OECD (2000).
These tests apply whether or not there is extra-binomial variance, but have somewhat lower power (Agresti 2002, Morgan 1992, Rao and Scott 1992, 1999, Fung et al.
Guidance Document on Aquatic Toxicity Testing of Difficult Substances and Mixtures.
1994, 1996).
Series on Testing and Assessment No.
First or Last Day of Hatch or Swim-up
Hutchinson, T. H. et al.
The response is an integer, giving the test day on which the indicated observation is observed for a given replicate tank.
76, str. 69–92.
The range of values is generally very limited and there are often high proportions of tied values, e.g. the same first day of hatch is observed in all control replicates and, perhaps in one or two low test concentrations.
114/Dop.
Parametric tests such as Williams and Dunnett are not appropriate for such data.
1: 106–14.
Unless there is evidence on serious non-monotonicity, the step-down Jonckheere-Terpstra test is very powerful for detecting effects of the test chemical.
Miles-Richardson, S. R. et al.
Otherwise, Dunn's test can be used.
47, 129–145.
Larval Abnormalities
Martinovic, D. et al.
The response is the count of larvae found to be abnormal in some way.
27, 478–488.
This response is frequently of low incidence and has some of the same problems as first day of hatch, as well as sometimes exhibiting erratic in concentration-response.
OECD (2012).
If the data at least roughly follow a monotone concentration shape, the step-down Jonckheere-Terpstra test is powerful for detecting effects.
OECD Conceptual Framework for Testing and Assessment of Endocrine Disrupters.
Series on Testing and Assessment, No. 54.
OECD Environmental Health and Safety Publications, Series on Testing and Assessment, št. 150, OECD, Pariz.
Organisation for Economic Co-operation and Development, OECD, Paris..
OKRAJŠAVE IN OPREDELITEV POJMOV
STATISTICAL GUIDANCE FOR REGRESSION ESTIMATES
snov ali zmes.
The observations used to fit a model are replicate means (length and weight) or replicate proportions (egg hatch and larval mortality) (OECD 2006).
koeficient variacije.
Weighted regression using replicate sample size as weight is generally advised.
encimski imunski test (ang.
Other weighting schemes are possible, such as weighting by predicted mean response or a combination of this and replicate sample size.
Enzyme-Linked Immunosorbent Assay).
Weighting by reciprocal of within-concentration sample variance is not recommended (Bunke et al.
Os HPG
1999, Seber and Wild, 2003, Motulsky and Christopoulos 2004, Huet et al.
os hipotalamus – hipofiza – spolne žleze.
2003).
Stopnja obremenitve
Any transformation of responses prior to analysis should preserve the independence of the observations and ECx and its confidence bounds should be expressed in the original units of measurement, rather than in transformed units.
mokra teža rib na prostornino vode.
For example, a 20 % change in the logarithm of length is not equivalent to a 20 % change in length (Lyles et.al 2008, Draper and Smith 1999).
najvišja tolerančna koncentracija, ki predstavlja približno 10 % LC50.
The flowchart in figure 4 gives an overview for ECx estimations.
Gostota rib
The details are described in the text below.
število rib na prostornino vode.
Figure 4
vitelogenin je fosfolipoglikobeljakovina in predstopnja beljakovin jajčnega rumenjaka, ki se običajno pojavi pri spolno aktivnih samicah vseh oviparnih vrst.
Flow chart for ECx Estimation of Replicate Mean Length, Weight, or Proportion of Egg Hatch or Larval Mortality, see text for more details Select a larget value of x or a different model
PRESKUSNI POGOJI ZA PRESEJALNI ENDOKRINI PRESKUS RIB
Is (a) predicted response at ECx within CI for control, or (b) predicted response within CI for predicted response at ECx or (c) CI for ECx too wide?
Vrsta preskusa
Compute 95 % CI for predicted response at control and at Ecx, Compute 95 % CI for ECx.
pretočni
Compare models using AICc criteria or professional judgement and select best fit
Temperatura vode
Assess goodness of fit of models: (a) visually, (b) compare predicted % effect to observed % effect, (c) compare control mean response to predicted mean response, (d) compare regression residual SS to pure error SS using F-test.
Kakovost osvetlitve
Reject poorly fitting models.
fluorescenčne sijalke (široki spekter)
8 or more concentrations plus control 6 or 7 concentrations plus control 5 concentrations plus control
Jakost svetlobe
Report model, ECx and its CI If no model and acceptable x can be found, report NOEC No Yes
10–20 μE/m2/s, 540–1000 luksov ali 50–100 ft-c (ravni v laboratoriju)
If no indication of extra-binominal variance, probit model can be fit to proportion data Also fit Brain-Cousins Hormetic model
12–16 ur svetlobe, 12–8 ur teme
Also fit OECD 4 & 5, Hill, Michaelis-Menton or other 3-5 parm model
< 5 g/l
For Bruce-Versteeg, simple exponential (OECD2), simple exponential w/shape parameter (OECD3) or other 2-3 parm model
Velikost preskusne komore
Considerations for Egg Hatch and Larval Mortality
10 l (vsaj)
For egg hatch and larval mortality, it is generally best to fit a decreasing model unless one is fitting a probit model as described below.
2 l (vsaj)
That is, one should model the proportion of eggs that do not hatch or larvae that die.
5 l (vsaj)
The reason for this is that ECx refers to a concentration at which there is a change equal to x % of the control mean response.
Količina preskusne raztopine
If there are 5 % control eggs that fail to hatch and one models failure to hatch, then EC20 refers to a concentration at which there is a change equal to 20 % of the 5 % control failure to hatch, and that is a change of 0,2 × 0,05 = 0,01 or 1 percentage point to 6 % failure to hatch.
8 l (vsaj)
Such a small change cannot be estimated in any meaningful way from the data available and is not biologically important.
1,5 l (vsaj)
Whereas if one models the proportion of eggs that hatch, the control proportion would be 95 % in this example and a 20 % reduction from the control mean would be a change of 0,95 × 0,2 = 0,18, so from 95 % hatch success to 77 % (= 95 – 18) hatching success and that effects concentration can be estimated and is presumably of greater interest.
4 l (vsaj)
This is not an issue with size measurements, though adverse effects on size generally mean a decrease in size.
Zamenjave količin preskusnih raztopin
Models for Size (length or weight) and Egg Hatch Success or Larval Survival.
vsaj 6 na dan
Except for the Brain-Cousens hormetic model, all of these models are described and recommended in OECD (2006).
vsaj 5 na dan
What are called OECD 2-5, are also discussed for ecotoxicity experiments in Slob (2002).
Starost preskusnih organizmov
There are, of course, many other models that might be useful.
glej odstavek 21
Bunke, et al.
Približna mokra teža odrasle ribe (g)
lists numerous models not included here and references to other models are plentiful.
samice: 1,5 ± 20 %
Those listed below are suggested as particularly appropriate in ecotoxicity experiments and widely used.
samci: 2,5 ± 20 %
With 5 test concentrations plus control
samice: 0,35 ± 20 %
Simple Exponential (OECD 2)
samci: 0,35 ± 20 %
Exponential with shape parameter (OECD 3)
samice: 0,65 ± 20 %
Simple Exponential with Lower Bound (OECD 4)
samci: 0,4 ± 20 %
With 6 or more test concentrations plus control
Št. rib na preskusno posodo
Exponential with shape parameter and lower bound (OECD 5)
6 (2 samca in 4 samice)
Where there is visual evidence of hormesis (unlikely with egg hatch success or larval survival, but sometimes observed in size observations)
6 (3 samci in 3 samice)
Brain-Cousens Hormetic; Brain and Cousens (1989)
10 (5 samcev in 5 samic)
Alternative models for egg hatch failure and larval mortality
Št. tretiranj
Increasing models for these responses can be fit by probit (or logistic) models if there is no evidence of extra-binomial variance and control incidence is estimated in the model fit.
= 3 (plus ustrezno št. kontrol)
This is not the preferred method, as it treats the individual, not the replicate, as the unit of analysis (Morgan 1992, O'Hara Hines and Lawless 1993, Collett 2002, 2003).
Št. posod na tretiranje
Goodness of fit of a single model
najmanj 4
Visually compare observed and predicted percent decrease at each test concentration (Motulsky and Christopoulos 2004, Draper and Smith 1999).
najmanj 2
Compare regression error mean square against the pure error mean square using an F-test (Draper and Smith 1999).
Št. rib na preskusno koncentracijo
Check that every term in the model is significantly different from zero (i.e., determine whether all model terms are important), (Motulsky and Christopoulos 2004).
16 odraslih samic in 8 samcev (4 samice in 2 samca v vsaki ponovitveni posodi)
Plots of residuals from regression vs. test concentration, possibly on a log(conc) scale.
12 odraslih samic in 12 samcev (3 samice in 3 samci v vsaki ponovitveni posodi)
There should be no pattern to this plot; the points should be randomly scattered about a horizontal line at zero height.
10 odraslih samic in 10 samcev (5 samice in 5 samcev v vsaki ponovitveni posodi)
The data should be evaluated for normality and variance homogeneity in the same way as indicated in Appendix 5.
Način hranjenja
In addition, normality of the residuals about the regression model should be assessed using the same methods indicated in Appendix 5 for the residuals from ANOVA
živi ali zamrznjeni odrasli solinski rakci ali njihovi navpliji dvakrat ali trikrat na dan (ad libitum), komercialno dostopna hrana ali kombinacija navedenega
Compare models
navpliji morskih rakcev dvakrat ali trikrat na dan (ad libitum), komercialno razpoložljiva hrana ali kombinacija navedenega
Use Akiake's AICc criteria.
navpliji solinskih rakcev dvakrat ali trikrat na dan (ad libitum), komercialno dostopna hrana ali kombinacija navedenega
Smaller AICc values denote better fits and if AICc(B)-AICc(A)≥10, the model A is almost certainly better than model B (Motulsky and Christopoulos (2004).
brez, razen če koncentracija raztopljenega kisika pade pod 60 % nasičenosti z zrakom