natgillin/translations-raw huggingface dataset:
To assess the risk to aquatic organisms from the use of veterinary medicinal products in gilts containing the synthetic steroidal hormone altrenogest, the MAHs conducted a Fish Full Life Cycle test to investigate and characterise the endocrine effects of this hormone, and also determined the PECsurfacewater from the use of the product as indicated in the summary of product characteristics (SPC), to establish if the concentrations expected in surface water would exceed the concentration known to cause a detrimental effect to aquatic populations of organisms in different representative EU scenarios (R1: Middle European land, R3: Middle European Mediterranean, and R4: Southern European Mediterranean).
Da bi ocenili tveganje za vodne organizme zaradi uporabe zdravil za uporabo v veterinarski medicini, ki vsebujejo sintetični steroidni hormon altrenogest, pri svinjah mladicah, so imetniki dovoljenja za promet z zdravilom izvedli preskus celotnega življenjskega kroga rib, s katerim so želeli preučiti in opredeliti endokrine učinke tega hormona, v njem pa so tudi določili vrednost PECpovršinska voda zaradi uporabe zdravila v skladu s povzetkom glavnih značilnosti zdravila, s čimer so želeli ugotoviti, ali bodo pričakovane koncentracije v površinski vodi presegle koncentracijo, ki ima škodljive učinke na vodne populacije organizmov v različnih reprezentativnih scenarijih v EU (R1: zemljišča v srednji Evropi, R3: srednje evropsko Sredozemlje in R4: južno evropsko Sredozemlje).
The PECsoil initial was further refined using the results from the anaerobic transformation study of altrengest in pig manure which determined that 26.5% accounted for non-extractable residues at day 45, and could be considered potentially bioavailable altrenogest or conjugates of altrenogest.
Začetna vrednost PECtla je bila dodatno izboljšana s pomočjo rezultatov iz študije o anaerobni pretvorbi altrenogesta v svinjskem gnoju, v kateri so odkrili, da je na 45. dan 26,5 % predstavljalo neizločljive ostanke, ki bi jih lahko šteli za morebitno biološko razpoložljiv altrenogest ali konjugate altrenogesta.
The CVMP notes that veterinary medicinal products containing altrenogest are also authorised for use in mares.
Odbor CVMP je upošteval, da so zdravila za uporabo v veterinarski medicini, ki vsebujejo altrenogest, odobrena tudi za uporabo pri kobilah.
Based on the available data, the marketing authorisation holders (MAHs) considered a worst-case scenario of renal elimination of altrenogest as the major route of excretion with 60% of the total dose of altrenogest being excreted in urine as altrenogest or altrenogest conjugates, and a total amount of 31% altrenogest-equivalents being excreted (considering complete deconjugation).
Na podlagi razpoložljivih podatkov so imetniki dovoljenja za promet z zdravilom upoštevali najslabši mogoči primer, pri katerem je glavna pot izločanja altrenogesta skozi ledvice, pri čemer se 60 % celotnega odmerka altrenogesta izloči z urinom kot altrenogest ali konjugati altrenogesta, 31 % ekvivalentov altrenogesta pa se izloči (ob upoštevanju popolne dekonjugacije).
Of the total radioactivity in bile, 6% was altrenogest (after multiple dose) and 14% altrenogest conjugates, corresponding to 4.5% to 10.5% of the total dose.
Od skupne radioaktivnosti v žolču je bilo 6 % altrenogesta (po večkratnih odmerkih) in 14 % konjugatov altrenogesta, kar predstavlja od 4,5 % do 10,5 % celotnega odmerka.
Ceva Animal Health Slovakia, s. r. o.
Češka republika Ceva Animal Health Slovakia, s. r. o.
Based on a PNEC <40 pg/l as well as the PECsurfacewater values from the scenarios above (release factor: 0.31, application rate of 0.094 g/ha) a risk was identified in STEP 4 for the R3 scenario (buffer zone 1-10 m), with risk quotients (RQs) of 3.29 (1 m), 2.84 (3 m), 2.59 (5 m), and 2.18 (10 m).
Na podlagi vrednosti PNEC <40 pg/l in vrednosti PECpovršinska voda iz zgornjih scenarijev (faktor sproščanja: 0,31, odmerek 0,094 g/ha) so odkrili tveganje pri 4. koraku za scenarij R3 (varovalni pas 1-10 m), s količniki tveganja (RQ) 3,29 (1 m), 2,84 (3 m), 2,59 (5 m) in 2,18 (10 m).
• the CVMP considered that in order to address the risk for fish and other aquatic organisms, risk mitigation measures should be included in the product information;
• odbor CVMP je upošteval, da je za obvladovanje tveganja za ribe in druge vodne organizme v informacije o zdravilu treba vključiti ukrepe za zmanjšanje tveganja;
The MAHs used this latter value (69% metabolism) for the PECsoil refinement.
Imetniki dovoljenja za promet z zdravilom so uporabili slednjo vrednost (69-odstotna presnova) za izboljšanje vrednosti PECtla.
Environmental risk assessment of altrenogest
Ocena tveganja altrenogesta za okolje
A fish life cycle test with zebrafish (Danio rerio), covering a complete fish generation (parental) and also part of the filial generation, was conducted to investigate the effects of a continuous exposure of altrenogest on different life stages, (including early life, juvenile growth, and reproduction stages of the parental generation, and early life stages of the filial generation).
Izveden je bil preskus življenjskega kroga rib s cebrico (Danio rerio), ki je zajel celotno (starševsko) generacijo rib in del generacije potomcev, da bi raziskali učinke neprekinjene izpostavljenosti altrenogestu na različne razvojne stopnje (vključno z zgodnjo razvojno stopnjo, mladiči in stopnjo razmnoževanja starševske generacije ter zgodnjo razvojno stopnjo generacije potomcev).
3 http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2011/03/WC500104495.pdf OECD guideline for the testing of chemicals 307
3 http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2011/03/WC500104495.pdf.
From the Fish Full Life Cycle no NOEC can be derived since significant population relevant effects have been shown already in the lowest concentration tested, i.e. 400 pg/l altrenogest (effects on fertilisation and F1 survival being the most sensitive developmental stages).
Iz preskusa celotnega življenjskega kroga rib ni bilo mogoče izpeljati vrednosti NOEC, ker so se pomembni učinki, bistveni za populacijo, pokazali že v najnižji preskušeni koncentraciji, tj. 400 pg/l altrenogesta (pri čemer sta bili oploditev in preživetje generacije F1 najobčutljivejši razvojni stopnji).
The MAHs make reference to the Council Directive 91/676/EEC concerning the protection of waters against pollution caused by nitrates from agricultural sources, which requires minimum distances to surface water which must be maintained when manure (or organic fertilizer) is spread onto cropland.
Imetniki dovoljenja za promet z zdravilom se sklicujejo na Direktivo Sveta 91/676/EGS o varstvu voda pred onesnaževanjem z nitrati iz kmetijskih virov, ki določa najmanjše razdalje, ki jih je treba obdržati do površinske vode, ko se gnoj (ali organsko gnojilo) nanaša na njivsko površino.
Of the total radioactivity in urine, 2% was identified as altrenogest and 24% as altrenogest conjugates, corresponding to 0.5% to 6% of the total dose.
Ugotovili so, da je bilo od skupne radioaktivnosti v urinu 2 % altrenogesta in 24 % konjugatov altrenogesta, kar predstavlja od 0,5 % do 6 % celotnega odmerka.
STEP 2 lead to a PECsurfacewater of 245 pg/l, and STEP 3 PECsurfacewater ranged between 16 to 219 pg/l depending on the scenarios considered, with scenario R3 having the highest PECsurfacewater value.
Vrednost PECpovršinska voda v 2. koraku je znašala 245 pg/l, vrednost PECpovršinska voda v 3. koraku pa je segala od 16 do 219 pg/l, odvisno od upoštevanih scenarijev, pri čemer je bila vrednost PECpovršinska voda najvišja pri scenariju R3.
The PECsoil initial was further refined with metabolism data (release rate 0.31%), and the rate of gilts that are integrated into the herd that is equivalent to the annual replacement rate (mean value 0.49).
Začetno vrednost PECtla so dodatno izboljšali s podatki o presnovi (hitrost sproščanja 0,31 %) in stopnjo svinj mladic, vključenih v čredo, ki je enakovredna letni nadomestitveni stopnji (srednja vrednost 0,49).
The environmental risk assessment is focused on the risk to the environment as a result of the zootechnical use of veterinary medicinal products containing altrenogest in gilts.
Poudarek ocene tveganja za okolje je na tveganju za okolje, ki je rezultat zootehnične uporabe zdravil za uporabo v veterinarski medicini, ki vsebujejo altrenogest, pri svinjah mladicah.
The PECsurfacewater was calculated according to FOCUS STEP 4, considering a DT50 value for soil of 6.5 days (geometric mean derived from four soils), an application rate of 0.000094 kg/ha, the result of the manure degradation study (factor: 0.265), the fraction of herd treatment (factor: 0.49) as well as the metabolism (factor: 0.31).
Vrednost PECpovršinska voda so izračunali v skladu s 4. korakom modela FOCUS, pri čemer so upoštevali vrednost DT50 za tla 6,5 dneva (geometrična srednja vrednost izhaja iz štirih tal), odmerek 0,000094 kg/ha, rezultat študije o razgradnji gnoja (faktor: 0,265), delež zdravljene črede (faktor: 0,49) in presnovo (faktor: 0,31).
These buffer zones are minimum distances to surface water which must be maintained when manure (or organic fertilizer) is spread onto cropland.
Ti varovalni pasovi pomenijo najkrajše razdalje, ki jih je treba obdržati do površinske vode, ko se gnoj (ali organsko gnojilo) nanaša na njivsko površino.
Using the scenario R4 (southern European Mediterranean) of the FOCUS STEP 4 modelling the maximum PECsurfacewater for a 1 m, 3 m, 5 m, and 10 m buffer zone were calculated, respectively, in relation to Directive 91/676/EEC6 concerning the protection of waters against pollution caused by nitrates from agricultural sources which is implemented in national law in the EU Member States.
Pri scenariju R4 (južno evropsko Sredozemlje) 4. koraka modela FOCUS so bile izračunane najvišje vrednosti PECpovršinska voda za metrski, trimetrski, petmetrski oziroma desetmetrski varovalni pas v povezavi z Direktivo 91/676/EGS6 o varstvu voda pred onesnaževanjem z nitrati iz kmetijskih virov, ki je prenesena v nacionalno zakonodajo držav članic EU.
List of the names, pharmaceutical forms, strengths of the veterinary medicinal products, animal species, route of administration, marketing authorisation holders in the Member States
Države članice, imetniki dovoljenja za promet, imena zdravila, mednarodno nelastniško ime, jakosti, farmacevtska oblike, živalske vrste, način in pot uporabe
A PNEC (Predicted No Effect Concentration) of <0.4 ng altrenogest/l was used for the risk assessment.
Za oceno tveganja je bila uporabljena predvidena koncentracija brez učinka (PNEC) < 0,4 ng altrenogesta/l.
In order to lower the risk to the aquatic environment associated with the use of veterinary medicinal products containing altrenogest to be administered orally to pigs the following risk mitigation measures are recommended to be included in the product information:
Da bi zmanjšali tveganje za vodno okolje, povezano z uporabo zdravil za uporabo v veterinarski medicini, ki vsebujejo altrenogest, za peroralno dajanje prašičem, je v informacije o zdravilu priporočeno vključiti naslednje ukrepe za zmanjšanje tveganja:
SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCT OR WASTE
- Posebni varnostni ukrepi za odstranjevanje neporabljenega zdravila ali odpadnih snovi
6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products {Invented name} should not enter water courses as this may be dangerous for fish and other aquatic organisms.
6.6 Posebni varnostni ukrepi za odstranjevanje neporabljenega zdravila ali odpadnih snovi {Izmišljeno ime} ne sme priti v vodne tokove, ker je to lahko nevarno za ribe in druge vodne organizme.
Fertilisation rate of the parental fish and post hatch survival of the filial generation were the most sensitive parameters, suggesting that the early life stages of the F1 generation and reproduction are the most sensitive
Stopnja oploditve starševskih rib in preživetje generacije potomcev po izvalitvi sta bila najobčutljivejša parametra, ki kažeta, da sta zgodnja razvojna stopnja generacije F1 in razmnoževanje tisti razvojni stopnji, ki sta najobčutljivejši na izpostavljenost altrenogestu.
• Based on the available data and conservative calculations, the CVMP considered that a risk for fish and other aquatic organisms associated with the zootechnical use of veterinary medicinal products containing altrenogest in gilts cannot be excluded for certain geographical areas;
• na podlagi razpoložljivih podatkov in konservativnih izračunov je odbor CVMP upošteval, da na nekaterih geografskih območjih ni mogoče izključiti tveganja za ribe in druge vodne organizme, povezanega z zootehnično uporabo zdravil za uporabo v veterinarski medicini, ki vsebujejo altrenogest, pri svinjah mladicah;
The amount of non-extractable residues (NER) formed after 45 days is used for the predicted environmental concentration in soil (PECsoil) refinement as this value is the closest to the half-maximal manure storage time for sows of 91 days, as explained in the CVMP guideline on the environmental impact assessment for veterinary medicinal products in support of the VICH guidelines GL6 and GL38 (EMEA/CVMP/ERA/418282/2005-Rev.1).
Količina neizločljivih ostankov (NER), nastala po 45 dneh, se uporablja za izboljšanje predvidene okoljske koncentracije v tleh (PECtla), ker je ta vrednost najbližja polovici najdaljšega časa shranjevanja gnoja za svinje, ki je 91 dni, kot je razloženo v smernici odbora CVMP o oceni vpliva zdravil za uporabo v veterinarski medicini na okolje v podporo smernicama VICH GL6 in GL38 (EMEA/CVMP/ERA/418282/2005-Rev.1).
According to the CVMP guideline on environmental impact assessment for veterinary medicinal products in support of VICH GL6 and GL381 when “adverse environmental effects are anticipated from the use of products, further assessment of possible exposure of the environment can be performed, even if straightforward application of the Phase I guidance would indicate exemption from further testing.” This provision implies that some products, which do not meet the trigger value for entering a Phase II environmental risk assessment (ERA), may however require further assessment to address specifically the concerns related to their activity and use.
V skladu s smernico CVMP o oceni vpliva zdravil za uporabo v veterinarski medicini na okolje v podporo smernicama VICH GL6 in GL381 velja, da ko „so pričakovani neugodni učinki na okolje zaradi uporabe zdravil, se lahko izvede dodatna ocena morebitne izpostavljenosti okolja, tudi če bi neposredna uporaba navodil iz I. faze pomenila izvzetje iz nadaljnjih testov".
1 CVMP guideline on environmental impact assessment for veterinary medicinal products in support of VICH GL6 and GL38 (EMEA/CVMP/ERA/418282/2005-Rev.1)http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/10/WC500004386.pdf 2 VICH GL6: Guideline on environmental impact assessment (EIAs) for veterinary medicinal products - Phase I http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/10/WC500004394.pdf
1 Smernica CVMP o oceni vpliva zdravil za uporabo v veterinarski medicini na okolje v podporo smernicama VICH GL6 in GL38 (EMEA/CVMP/ERA/418282/2005-Rev.1)http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/10/WC500004386.pdf.
R4 is often used to cover a conservative run-off scenario in FOCUS-SW and consequently has been used for the exposure assessment for the FOCUS-SW STEP 3 calculations.
konservativen scenarij površinskega odtoka, zato so ga uporabili za oceno izpostavljenosti pri izračunih v 3. koraku poročila FOCUS-SW.
The CVMP acknowledged these results, but concluded that data on the metabolism of altrenogest in gilts, indicating a total amount of excreted altrenogest equivalents corresponding to 5% to 16.5% (release factor 0.05-0.15) of the total dose, should have been considered instead of the release factor of 0.31, given the reliability and quality of the study and its results being in line with existing literature data for progestogens and also with residue concentrations found in liver and kidney of pigs.
Odbor CVMP je potrdil te rezultate, vendar je zaključil, da bi bilo glede na zanesljivost in kakovost študije, katere rezultati so bili v skladu z obstoječimi podatki iz literature o progestogenih in tudi s koncentracijami ostankov, najdenih v jetrih in ledvicah prašičev, treba upoštevati podatke o presnovi altrenogesta pri svinjah mladicah, ki kažejo celotno količino izločenih ekvivalentov altrenogesta, ki znaša od 5 % do 16,5 % (faktor sproščanja 0,05-0,15) celotnega odmerka, in ne faktor sproščanja 0,31.
However it was agreed that risk mitigation measures need to be included in the product information for veterinary medicinal products containing altrenogest to be administered orally to pigs to lower the risk to the environment and to make the user aware that altrenogest may be hazardous for fish and other aquatic organisms.
Kljub temu je bilo dogovorjeno, da je treba v informacije o zdravilih za uporabo v veterinarski medicini, ki vsebujejo altrenogest, za peroralno dajanje prašičem, vključiti ukrepe za zmanjšanje tveganja, da se zmanjša tveganje za okolje in ozavesti uporabnike, da je altrenogest lahko nevaren za ribe in druge vodne organizme.
The DT50 values for soils 1, 2, 3 and 4 are 23.7, 5.3, 2.0, and
Vrednosti DT50 za tla 1, 2, 3 in 4 znašajo 23,7, 5,3, 2,0 oziroma 4,6 dneva, iz česar izhaja, da geometrična srednja vrednost DT50 znaša 5,8 dneva.
For surface water the FOCUS STEP 2 and 3 (Phase IIA), were conducted as the STEP 1 resulted in a PECsurfacewater larger than the lowest predicted no effect concentration (PNEC) (0.4 ng/l).
A faza), ker je bila vrednost PECpovršinska voda v 1. koraku višja od najnižje predvidene koncentracije brez učinka (PNEC) (0,4 ng/l).
Poland Virbac S.A. 1ère avenue
Češka republika Virbac S.A. 1ère avenue
{Invented name} should not enter water courses as this may be dangerous for fish and other aquatic organisms.
{Izmišljeno ime} ne sme priti v vodne tokove, ker je to lahko nevarno za ribe in druge vodne organizme
• the CVMP considered that the overall benefit-risk balance is positive for veterinary medicinal products containing altrenogest to be administered orally to pigs and horses; the CVMP recommended variations of the marketing authorisations for veterinary medicinal products containing altrenogest to be administered orally to pigs (see Annex I) in order to amend the summaries of product characteristics, labelling and package leaflets in line with recommended changes in the product information as set out in Annex III.
je odbor CVMP priporočil spremembo dovoljenj za promet z zdravili za uporabo v veterinarski medicini, ki vsebujejo altrenogest, za peroralno dajanje prašičem (glejte Prilogo I), da se spremenijo povzetek glavnih značilnosti zdravila, označevanje in navodilo za uporabo v skladu s priporočenimi spremembami informacij o zdravilu, opredeljenimi v Prilogi III.
The PECgroundwater (Phase IIA STEP 1) was calculated using the recommended stepwise approach described in the CVMP guideline on environmental impact assessment for veterinary medicinal products in support of the VICH guidelines GL6 and GL 38 (EMEA/CVMP/418282/2005-Rev.1), STEP 1 to STEP 3.
A faza, 1. korak) je bila izračunana s pomočjo priporočenega postopnega pristopa, opisanega v smernici odbora CVMP o oceni vpliva zdravil za uporabo v veterinarski medicini na okolje v podporo smernicama VICH GL6 in GL38 (EMEA/CVMP/418282/2005-Rev.1), od 1. koraka do 3. koraka.
Amendments in the relevant sections of the summary of product characteristics, labelling and package leaflet
Dopolnitve v ustreznih poglavjih v SPC, Označevanju in Navodilu za uporabo
Based on the available data and conservative calculations, a risk for fish and other aquatic organisms associated with the zootechnical use of veterinary medicinal products containing altrenogest in gilts cannot be excluded for certain geographical areas (i.e. Middle European Mediterranean).
Na podlagi razpoložljivih podatkov in konservativnih izračunov na nekaterih geografskih območjih (tj. v srednjem evropskem Sredozemlju) ni mogoče izključiti tveganja za ribe in druge vodne organizme, povezanega z zootehnično uporabo zdravil za uporabo v veterinarski medicini, ki vsebujejo altrenogest, pri svinjah mladicah.
Risk mitigation measures are recommended in the product information for veterinary medicinal products containing altrenogest to be administered orally to pigs to lower the risk to the environment and to make the user aware that altrenogest may be hazardous for fish and other aquatic organisms.
V informacije o zdravilih za uporabo v veterinarski medicini, ki vsebujejo altrenogest, za peroralno dajanje prašičem, je priporočeno vključiti ukrepe za zmanjšanje tveganja, da se zmanjša tveganje za okolje in ozavesti uporabnike, da je altrenogest lahko nevaren za ribe in druge vodne organizme.
Consequently the use of altrenogest in mares is not considered to pose a risk to the environment when used as specified in the SPCs given the minimal environmental exposure associated with this use, and the environmental risk assessment presented below is based on the use of altrenogest in gilts.
Zato uporaba altrenogesta pri kobilah ne pomeni tveganja za okolje, ko se uporablja v skladu s povzetki glavnih značilnosti zdravila, ker je izpostavljenost okolja pri taki uporabi minimalna.
A Phase I and a Phase II environmental risk assessment were conducted.
faza ocene tveganja za okolje.
SPC section 4.5 Special precautions for use.
Povzetek glavnih značilnosti zdravila, poglavje 4.5 - Posebni previdnostni ukrepi
5 OECD 54 guideline on Current Approaches in the Statistical Analysis of Ecotoxicity Data: A Guidance to Application http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=env/jm/mono%282006%2918&doclanguage =en http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:31991L0676&from=en relevant for winter cereals, as proposed by the FOCUS-SW report and need to be calculated as well.
5 Smernica OECD št. 54 „Trenutni pristopi k statistični analizi podatkov o ekotoksičnosti: navodila za uporabo“ (2006)http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=env/jm/mono%282006%2918&doclanguage =en.
Environmental fate studies
Študije obnašanja v okolju
MATERIALS, IF ANY {Invented name} should not enter water courses as this may be dangerous for fish and other aquatic organisms.
ALI ODPADNIH SNOVI, ČE OBSTAJAJO {Izmišljeno ime} ne sme priti v vodne tokove, ker je to lahko nevarno za ribe in druge vodne organizme.
The MAHs proposes the following risk mitigation measure: “When spreading manure from treated animals, the minimum distance to surface water as defined in the national or local regulations has to be strictly respected, because the manure may contain altrenogest which could cause adverse effects in the aquatic environment”.
Imetniki dovoljenja za promet z zdravilom predlagajo naslednji ukrep za zmanjšanje tveganja: „Pri nanašanju gnoja zdravljenih živali je treba natančno upoštevati najmanjšo razdaljo do površinske vode, kot jo določajo nacionalni ali lokalni predpisi, ker lahko gnoj vsebuje altrenogest, ki bi v vodnem okolju lahko povzročil škodljive učinke.“
For the Phase I the PECsoil initial for gilts, sows and mares was established using the daily doses and the default values from the CVMP guideline on environmental impact assessment for veterinary medicinal products in support of the VICH guidelines GL6 and GL 38 (EMEA/CVMP/418282/2005Rev.1).
Začetna vrednost PECtla za svinje mladice, svinje in kobile za I. fazo je bila določena s pomočjo dnevnih odmerkov in privzetih vrednosti iz smernice odbora CVMP o oceni vpliva zdravil za uporabo v veterinarski medicini na okolje v podporo smernicama VICH GL6 in GL38 (EMEA/CVMP/418282/2005-Rev.1).