natgillin/translations-raw huggingface dataset:
Thus, uptake and depuration rate constants can be estimated with a minimum of sampling points, and the kinetic BCF derived.
Orgaanilise süsiniku üldsisaldus
The initial purpose of examining alternative designs for BCF studies was to develop a small test to be used in an intermediate testing step to refute or confirm BCF estimates based on KOW and QSARs and so eliminate the need for a full study for many substances, and to minimise cost and animal use via reduction in sampling and in the number of analytical sequences performed.
2 mg/l
While following the main design of the previous test method to allow integration of test results with existing BCF data, and to ease performance of testing and data interpretation, the aim was to provide BCF estimates of adequate accuracy and precision for risk assessment decisions.
Ioniseerimata ammoniaak
Substances that would be eligible for the minimised test design should belong to the general domain that this test method was developed for, i.e. non-polar organic substances (cf. paragraph 49).
Kloorijäägid
If there is any indication that the substance to be tested might show a different behaviour (e.g. a clear deviation from first-order kinetics), a full test should be conducted for regulatory purposes.
10 μg/l
Typically, the minimised test is not run over a shorter period than the standard BCF test, but comprises less fish sampling (see Appendix 6 for the rationale).
Fosfororgaaniliste pestitsiidide üldsisaldus
However, the depuration period may be shortened for rapidly depurating substances to avoid concentrations in the fish falling below the limit of detection/quantification before the end of the test.
50 ng/l
A minimised exposure fish test with a single concentration can be used to determine the need for a full test, and if the resulting data used to calculate rate constants and BCF are robust (cf. paragraph 93), the full test may be waived if the resulting BCF is far from regulatory values of concern.
Kloororgaaniliste pestitsiidide ja polüklooritud bifenüülide summaarne üldsisaldus
In some cases, it may be advantageous to perform the minimised test design with more than one test concentration as a preliminary test to determine whether BCF estimates for a substance are concentration dependent.
Orgaanilistes ühendites sisalduva kloori üldsisaldus
If the BCF estimates from the minimised test show concentration dependence, the performance of the full test will be necessary.
25 ng/l
If, based on such a minimised test, BCF estimates are not concentration dependent but the results are not considered definitive, then any subsequent full test could be performed at a single concentration, thereby reducing animal use in comparison to a two (or more) concentration full test.
Alumiinium
Substances potentially eligible for the minimised test should:
Arseen
Be likely to exhibit approximate first order uptake and depuration kinetics, e.g. derived from read-across with similar substances;
Kroom
Have a log KOW < 6 unless rapid metabolism is expected [40];
Koobalt
Be sufficiently water-soluble with respect to the analytical technique (cf. paragraph 24);
Vask
Be clearly quantifiable (i.e. concentrations should be at least one order of magnitude above the limit of quantification), both in fish and water, radioactive labelling is recommended (cf. paragraph 23); and
Raud
Have a depuration period greater than its predicted half-life (cf. Appendix 5 for calculations), or the duration of depuration should be adjusted accordingly (cf. paragraph 91).
Plii
An exception to this rule is allowed if rapid metabolism of the substance is expected.
Nikkel
SAMPLING SCHEDULE FOR STUDIES FOLLOWING THE MINIMISED DESIGN
Tsink
Fish sampling
Kaadmium
Fish sampling is reduced to four sampling points:
100 ng/l
At the middle and end of the uptake phase (the latter being the beginning of depuration as well), e.g. after 14 and 28 days (33).
Elavhõbe
At the middle of the depuration phase and at termination of the study (where substance concentration is < 10 % of the maximum concentration, or at least clearly past one half-life of the substance), e.g. after 7 and 14 days of depuration (33).
Hõbe
If rapid depuration is expected or observed, it may be necessary to shorten the depuration period to avoid concentrations in the fish falling below the limit of quantification.
KATSE JAOKS SOOVITATAVAD KALALIIGID
Lipid measurement as in full study.
Soovitatav liik
Growth correction as in full study.
Soovitatav katsetemperatuuride vahemik (°C)
The BCF is calculated as a kinetic BCF.
Soovitatav katselooma üldpikkus (cm) [2]
Design modifications
(Linnaeus) – harilik karpkala
Taking into account the test substance properties, valid QSAR predictions and the specific purpose of the study, some modifications in the design of the study can be considered:
(Temminck & Schlegel) – jaapani riisikala
If greater precision is needed, more fish (6 or 8 instead of 4) could be used for the sample at the end of the uptake phase.
(Peters) – gupi
Inclusion of an ‘extra’ group of fish to be used if depuration at 14 days (or the predicted end of the depuration phase) has not been sufficient for adequate depuration (i.e. > 50 %).
(Rafinesque) – sinilõpuseline päikeseahven
If the predicted duration of the depuration phase is shorter or longer than 14 days, the sampling schedule should be adapted (i.e. one group of fish at the predicted end of the depuration phase, and one group after half that time).
(Walbaum) – vikerforell
Use of two test concentrations to explore possible concentration dependence.
(Linnaeus) – harilik ogalik
If the results of the minimised test, conducted with two test concentrations, show that the BCF is not concentration dependent (i.e. differ less than 20 %), one test concentration may be considered sufficient in a full test, if it is conducted.
18–20
It seems likely that models of bioaccumulation processes such as those proposed by Arnot et al.
Harvemini on kasutatud näiteks järgmisi suudmeala- ja merekalu.
can be used to assist in planning the length of uptake and depuration phases (see also Appendix 5).
Kotkaskalalane
Calculations
Hammaskarp
The rationale for this approach is that the bioconcentration factor in a full test can either be determined as a steady-state bioconcentration factor (BCFSS) by calculating the ratio of the concentration of the test substance in the fish's tissue to the concentration of the test substance in the water, or by calculating the kinetic bioconcentration factor (BCFK) as the ratio of the uptake rate constant k1 to the depuration rate constant k2.
Hõbeateriin
The BCFK is valid even if a steady-state concentration of a substance is not achieved during uptake, provided that uptake and depuration act approximately according to first order kinetic processes.
Punnkõht
As an absolute minimum two data points are required to estimate uptake and depuration rate constants, one at the end of the uptake phase (i.e. at the beginning of the depuration phase) and one at the end (or after a significant part) of the depuration phase.
Inglise merikeel
The intermediate sampling point is recommended as a check on the uptake and depuration kinetics [41].
Sarvikvõldas
For calculations, see Appendixes 5 and 6.Interpretation of the results
Harilik ogalik
To assess the validity and informative value of the test, verify that the depuration period exceeds one half-life.
Harilik huntahven
Also, the BCFKm (kinetic BCF derived from a minimised test) should be compared to the minimised BCFSS value (which is the BCFSS calculated at the end of the uptake phase, assuming that steady-state has been reached.
Harilik viidikas
This can only be assumed, as the number of sampling points is not sufficient for proving this).
Eespool tabelis loetletud mageveekalu on lihtne kasvatada ja/või nad on aastaringselt laialdaselt kättesaadavad, ent suudmeala- ja mereliikide kättesaadavus on osaliselt piiratud konkreetsete riikidega.
If the BCFKm < minimised BCFSS, the minimised BCFSS should be the preferred value.
Nimetatud kalu saab kasvatada ja kultiveerida kalakasvanduses või laboris haiguste ja parasiitide suhtes kontrollitud tingimustes nii, et katseloomad on terved ja nende põlvnemine on teada.
If BCFKm is less than 70 % of the minimised BCFSS, the results are not valid, and a full test should be conducted.
Need kalad on kättesaadavad paljudes maailma piirkondades.
If the minimised test gives a BCFKm in the region of any value of regulatory concern, a full test should be conducted.
Tuleks silmas pidada, et katses kasutatakse suuruse näitajana ja kasvu kiiruskonstandi leidmiseks soovitatavalt massi.
If the result is far from any regulatory value of concern (well above or below), a full test may not be necessary, or a single concentration full test may be conducted if required by the relevant regulatory framework.
Samas mööndakse, et praktikas on hõlpsam kasutada pikkust, kui kalu tuleb katse alguses (st lähtepopulatsioonist) valida silma järgi.
If a full test is found to be necessary after a minimised test at one concentration, this can be conducted at a second concentration.
See pikkusevahemik on esitatud Jaapanis kehtival kemikaalide kontrollimise seadusel põhinevates katsemeetodites uute kemikaalide jmt jaoks.
If the results are consistent, a further full test at a different concentration can be waived, as the bioconcentration of the substance is not expected to be concentration dependent.
Teoreetiline näide proovivõtukavast täismahus tehtavas veekaudsel kokkupuutel biokontsentreerumise katses, milles uuritava aine log KOW = 4.
If the minimised test has been conducted at two concentrations, and the results show no concentration dependence, the full test may be conducted with only one concentration (cf. paragraph 87).
Veeproovide arv [1]
The test report for the minimised test should include all the information demanded for the full test (cf. paragraph 81), except that which is not possible to elaborate (i.e. a curve showing the time to steady-state and the steady-state bioconcentration factor; for the latter the minimised BCFss should be given instead).
(4 + 3 [6])
Additionally, it should also include the reasoning for using the minimised test and the resulting BCFKm.
KOKKU
C.13 - III: Dietary Exposure Bioaccumulation Fish Test
Teoreetiline näide proovivõtukavast aine toidukaudse bioakumuleerumise katses, kus omastamisetapi kestus on 10 päeva ja puhastumisetapi kestus 42 päeva.
The method described in this section should be used for substances where the aqueous exposure methodology is not practicable (for example because stable, measurable water concentrations cannot be maintained, or adequate body burdens cannot be achieved within 60 days of exposure; see previous sections on the aqueous exposure method).
Võetav proov
It should be realised though that the endpoint from this test will be a dietary biomagnification factor (BMF) rather than a bioconcentration factor (BCF) [42].
Proovivõtu ajakava
In May 2001 a new method for the bioaccumulation testing of poorly water soluble organic substances was presented at the SETAC Europe conference held in Madrid (36).
Söödaproovide arv
This work built on various reported bioaccumulation studies in the literature using a dosing method involving spiked feed (e.g. (37)).
Kalade arv proovi kohta
Early in 2004 a draft protocol (38), designed to measure the bioaccumulation potential of poorly water soluble organic substances for which the standard water exposure bioconcentration method was not practicable, together with a supporting background document (39), was submitted to an EU PBT working group.
Etapi päev
Further justification given for the method was that potential environmental exposure to such poorly soluble substances (i.e. log KOW >5) may be largely via the diet (cf. (40) (41) (42) (43) (44)).
Täiendav kalaproov?
For this reason, dietary exposure tests are referred to in some published chemicals regulations [43].
Katserühm
It should be realised however, that in the method described here exposure via the aqueous phase is carefully avoided and thus a BMF value from this test method cannot directly be compared to a BMF value from a field study (in which both water and dietary exposure may be combined).
Kontrollrühm
This section of the present test method is based on this protocol (38) and is a new method that did not appear in the previous version of TM C.13.
Omastamisetapp
This alternative test allows the dietary exposure pathway to be directly investigated under controlled laboratory conditions.
3 – katserühmast
Potential investigators should refer to paragraphs 1 to 14 of this test method for information on when the dietary exposure test may be preferred over the aqueous exposure test.
3 – kontrollrühmast [7]
Information on the various substance considerations is laid out, and should be considered before a test is conducted.
Jah [10]
The use of radiolabelled test substances can be considered with similar considerations as for the aqueous exposure method (cf. paragraphs 6 and 65).
Puhastumisetapp
The dietary method can be used to test more than one substance in a single test, so long as certain criteria are fulfilled; these are explored further in paragraph 112.
Märkus etappide kestuse ja proovivõtuaegade kohta: omastamisetapp algab rikastatud sööda esmakordse andmise hetkel.
For simplicity the methodology here describes a test using only one test substance.
Katsepäev kestab ühest söötmiskorrast kuni hetkeni veidi enne järgmist söötmiskorda 24 tundi hiljem.
The dietary test is similar to the aqueous exposure method in many respects with the obvious exception of the exposure route.
Esimene proov (tabelis tähistatud numbriga 1) tuleks võtta veidi (nt üks tund) enne esmakordset söötmist.
Hence many aspects of the method described here overlap with the aqueous exposure method described in the previous section.
Proovid tuleks kogu katse vältel ideaaljuhul võtta veidi enne järgmise päeva söötmiskorda (st umbes 23 tundi pärast proovivõtupäeva söötmiskorda).
Cross-reference to relevant paragraphs in the previous section has been made as far as possible, but in the interests of readability and understanding a certain amount of duplication is unavoidable.
Omastamisetapp lõpeb veidi enne esmakordset rikastamata söödaga söötmist, mis tähistab puhastumisetapi algust (eeldatavalt jätkavad katserühma kalad 24 tunni jooksul pärast viimast rikastatud söödaga söötmist rikastatud sööda seedimist).
Flow-through or semi-static conditions can be employed (cf. paragraph 4); flow-through conditions are recommended to limit potential exposure of test substance via water as a result of any desorption from spiked food or faeces.
Seepärast tuleks omastamisetapi lõpus võetav proov võtta veidi enne esmakordset rikastatud söödaga söötmist ja puhastumisetapi esimene proov umbes 23 tundi pärast esmakordset rikastatud söödaga söötmist.
The test consists of two phases: uptake (test substance-spiked feed) and depuration (clean, untreated feed) (cf. paragraph 16).
Sulgudes on esitatud lisaproovide võtmise korral analüüsitavate veeproovide või kalade arv.
In the uptake phase, a “test” group of fish are fed a set diet of a commercial fish food of known composition, spiked with the test substance, on a daily basis.
Katse eel arvutatud hinnanguline k2 väärtus log KOW väärtusel 4,0 on 0,652 päeva kohta.
Fish ideally should consume all of the offered food (c.f. paragraph 141).
Katse kavandatud üldkestus on 3 × tSS = 3 × 4,6 päeva, s.o 14 päeva.
Fish are then fed the pure, untreated commercial fish food during the depuration phase.
Näitaja tSS-i hindamist on käsitletud 5. liites.
As for the aqueous exposure method, more than one test group with different spiked test substance concentrations can be used if necessary, but for the majority of highly hydrophobic organic test substances one test group is sufficient (cf. paragraphs 49 and 107).
Veeproov võetakse pärast seda, kui vesi on vahetunud vähemalt kolmekordses kambri mahus.
If semi-static conditions are used fish should be transferred to a new medium and/or a new test chamber at the end of the uptake phase (in case the medium and/or apparatus used in the uptake phase has been contaminated with the test substance through leaching).
Need kalad võetakse lähtepopulatsioonist.
The concentrations of the test substance in the fish are measured in both phases of the test.
Kui suurema täpsuse saavutamiseks või metabolismiuuringute tegemiseks on vaja suuremat arvu kalu, tuleks täiendavalt vajaminevad kalad võtta omastamisetapi ja puhastumisetapi lõpus (vt punkt 40).
In addition to the group of fish fed the spiked diet (the test group), a control group of fish is held under identical conditions and fed identically except that the commercial fish food diet is not spiked with test substance.
Lipiidisisalduse analüüsimiseks võib olla täiendavalt vaja vähemalt 3 kala, kui selleks ei ole võimalik kasutada kalu, kes valiti aine sisalduse määramiseks katse alguses, omastamisetapi lõpus ja puhastumisetapi lõpus.
This control group allows background levels of test substance to be quantified in unexposed fish and serves as a comparison for any treatment-related adverse effects noted in the test group(s) [44].
Tuleb silmas pidada, et paljudel juhtudel peaks olema võimalik kasutada selleks otstarbeks üksnes 3 kontrollrühmast võetud kala (vt punkt 56).
It also allows comparison of growth rate constants between groups as a check that similar quantities of offered diet have been consumed (potential differences in palatability between diets should also be considered in explaining different growth rate constants; cf. paragraph 138).
Uuritava aine ja lipiidide sisalduse suhtes analüüsitakse nii kontrollrühmast kui ka katserühmast 3 söödaproovi.
It is important that during both the uptake and depuration phases, diets of nutritional equivalency are fed to the test and control groups.
Kalaproov võetakse lähtepopulatsioonist uuringu algushetkele võimalikult lähedasel hetkel; lähtepopulatsioonist tuleks lipiidisisalduse suhtes analüüsimiseks võtta katse alguses vähemalt 3 kala.
An uptake phase that lasts 7-14 days is generally sufficient, based on experience from the method developers (38) (39).
Omastamisetapi algusjärgus (soovi korral) võetavatest proovidest saadud andmed võimaldavad arvutada uuritava aine toidust imendumise määra, mida saab võrrelda puhastumisetapi andmete põhjal arvutatud imendumistõhususe väärtusega.
This range should minimise the cost of undertaking the test whilst still ensuring sufficient exposure for most substances.
Koespetsiifilise analüüsi jaoks võib võtta veel 5 kala.
However, in some cases the uptake phase may be extended (cf. paragraph 127).
Tuleb silmas pidada, et paljudel juhtudel peaks olema võimalik kasutada selleks otstarbeks üksnes 3 kontrollrühmast võetud kala (vt punktid 56 ja 153).
During the uptake phase the substance concentration in the fish may not reach steady-state so data treatment and results from this method are usually based on a kinetic analysis of tissue residues.
ÜLDISED ARVUTUSED
(Note: Equations for estimating time to steady-state can be applied here as for the aqueous exposure test — see Appendix 5).
Sissejuhatus
The depuration phase begins when the fish are first fed unspiked diet and typically lasts for up to 28 days or until the test substance can no longer be quantified in whole fish, whichever is the sooner.
Omastamisetapi kestuse hindamine
The depuration phase can be shortened or lengthened beyond 28 days, depending on the change with time in measured chemical concentrations and fish size.
Puhastumisetapi kestuse hindamine
This method allows the determination of the substance-specific half-life (t1/2, from the depuration rate constant, k2), the assimilation efficiency (absorption across the gut; a), the kinetic dietary biomagnification factor (BMFK), the growth-corrected kinetic dietary biomagnification factor (BMFKg), and the lipid-corrected [45] kinetic dietary biomagnification factor (BMF KL) (and/or the growth- and lipid-corrected kinetic dietary biomagnification factor, BMFKgL) for the test substance in fish.
Järjestikuse analüüsi meetod: puhastumise (kao) kiiruskonstandi k2 määramine
As for the aqueous exposure method, increase in fish mass during the test will result in dilution of test substance in growing fish and thus the (kinetic) BMF will be underestimated if not corrected for growth (cf .paragraphs 162 and 163).
Järjestikuse analüüsi meetod: omastamise kiiruskonstandi k1 määramine (üksnes veekaudse kokkupuute meetodi puhul)
In addition, if it is estimated that steady-state was reached in the uptake phase an indicative steady-state BMF can be calculated.
Omastamise ja puhastumise (kao) kiiruskonstantide üheaegse arvutamise meetod (üksnes veekaudse kokkupuute meetodi puhul)
Approaches are available that make it feasible to estimate a kinetic bioconcentration factor (BCFK) from data generated in the dietary study (e.g. (44) (45) (46) (47) (48).
Kineetilise BCF-i ja BMF-i korrigeerimine kasvust tingitud lahjenemise suhtes
Pros and cons of such approaches are discussed in Appendix 8.
Lipiidisisalduse suhtes normaliseerimine lähtuvalt lipiidisisaldusest 5 % (üksnes veekaudse kokkupuute meetodi puhul)
The test was designed primarily for poorly soluble non-polar organic substances that follow approximately first order uptake and depuration kinetics in fish.
Veekaudse kalades bioakumuleerumise üldmudel on kirjeldatav omastamise ja kaoga seotud protsesside kaudu; sealjuures ei võeta arvesse toidu kaudu omastamist.
In case a substance is tested that does not follow approximately first order uptake and depuration kinetics, then more complex models should be employed (see references in Appendix 5) and advice from a biostatistician and/or pharmacokineticist sought.
Diferentsiaalvõrrand (dCf/dt), millega kirjeldatakse aine sisalduse muutumise kiirust kalas (mg/kg– 1 päevas– 1), on järgmine (1):
The BMF is normally determined using test substance analysis of whole fish (wet weight basis).
[võrrand A5.1],
If relevant for the objectives of the study, specific tissues (e.g. muscle, liver) can be sampled if the fish is divided into edible and non-edible parts (cf. paragraph 21).
kus
Furthermore, removal and separate analysis of the gastrointestinal tract may be employed to determine the contribution to whole fish concentrations for sample points at the end of the uptake phase and near the beginning of the depuration phase, or as part of a mass balance approach.
on aine kalas omastamist iseloomustav esimest järku reaktsiooni kiiruskonstant (l/kg päevas),
Lipid content of sampled whole fish should be measured so that concentrations can be lipid-corrected, taking account of lipid content of both the diet and the fish (cf. paragraphs 56 and 57, and Appendix 7).
on kalas toimuvat ainest puhastumist iseloomustav esimest järku reaktsiooni kiiruskonstant (päeva kohta),
Fish weight of sampled individuals should be measured and recorded, and be linked to the analysed chemical concentration for that individual (e.g. reported using a unique identifier code for each fish sampled), for the purpose of calculating growth that may occur during the test.
on kala kasvu (kasvust tingitud lahjenemist) iseloomustav esimest järku reaktsiooni kiiruskonstant (päeva kohta),
Fish total length should also be measured where possible [46].
on metaboliseerumist iseloomustav esimest järku reaktsiooni kiiruskonstant (päeva kohta),
Weight data are also necessary for estimating BCF using depuration data from the dietary test.
on roojamist iseloomustav esimest järku reaktsiooni kiiruskonstant (päeva kohta),
Information on the test substance as described in paragraphs 3 and 22 should be available.
on kontsentratsioon vees (mg/l) ja
An analytical method for test substance concentrations in water is not usually necessary; methods with suitable sensitivity for measuring concentrations in fish food and fish tissue are required.
on kontsentratsioon kalas (mg/kg märgmassi alusel).
The method can be used to test more than one substance in a single test.
Bioakumuleeruvate ainete puhul võib eeldada, et kõige asjakohasem lubatud kõikumise (vt punkt 24) piiresse jääv kokkupuutekontsentratsioon vees (Cw) on ajaga kaalutud keskmine kontsentratsioon.