natgillin/translations-raw huggingface dataset:
Indtræffer der endnu et dødsfald, skal doseringen straks indstilles, og ingen yderligere dyr doseres, Da optræden af endnu et dødsfald (uanset det testede antal dyr på ophørstidspunktet) falder ind under udfald A (to eller flere dødsfald), følger man klassificeringsreglen i bilag 2 ved fast dosis 5 mg/kg (dvs. kategori 1. hvis der er to eller flere dødsfald, og kategori 2 hvis der er højst et dødsfald), Derudover indeholder bilag 4 vejledning i, hvordan man foretager klassificeringen i EU's system, indtil det nye GHS er indført.
Because the occurrence of a second death (irrespective of the number of animals tested at the time of termination) falls into outcome A (two or more deaths), the classification rule of Appendix 2 at the 5 mg/kg fixed dose is followed (Category 1 if there are two or more deaths or Category 2 if there is no more than one death). In addition, Appendix 4 gives guidance on the classification in the EU system until the new GHS is implemented.
Oplysninger om teststoffets giftighed kan fås ud fra viden om tilsvarende testede stoffer eller tilsvarende testede blandinger eller produkter, idet der tages hensyn til art og procentuelt indhold af de stoffer, der vides at være af toksikologisk betydning, Når der foreligger få eller slet ingen oplysninger om teststoffets toksicitet, eller når stoffet forventes at være toksisk, skal hovedundersøgelsen udføres.
Information about the toxicity of the test material can be gained from knowledge about similar tested compounds or similar tested mixtures or products, taking into consideration the identity and percentage of components known to be of toxicological significance. In those situations where there is little or no information about its toxicity, or in which the test material is expected to be toxic, the main test should be performed.
Imidlertid bør observationsperioden ikke fastsættes ufravigeligt, Den bør fastlægges ud fra de toksiske reaktioners indsætten og restitutionsperiodens længde og kan således forlænges, når det skønnes nødvendigt.
However, the duration of observation should not be fixed rigidly. It should be determined by the toxic reactions, time of onset and length of recovery period, and may thus be extended when considered necessary.
Tidspunkterne for toksiske symptomers indsætten og forsvinden er vigtige, navnlig hvis der er tendens til forsinkede toksiske symptomer (11), Alle observationer registreres systematisk, og der føres individuel protokol for hvert dyr.
The times at which signs of toxicity appear and disappear are important, especially if there is a tendency for toxic signs to be delayed (11). All observations are systematically recorded, with individual records being maintained for each animal.
Stallard, N., Whitehead, A. and Ridgeway, P. (2002), Statistical evaluation of the revised fixed dose procediire.-Hum, Exp.
Stallard, N., Whitehead, A and Ridgeway, P. (2002) Statistical evaluation of the revised fixed dose procedure. Hum. Exp.
Paris.
Paris
Principles und Methods of Toxicology.
Principles and Methods of Toxicology.
≥ 2 dødsfald
≥ 1 with evident toxicity and / or 1 death No evident toxicity and no death Group size
De 5 dyr i hver gruppe i hovedundersøgelsen skal indbefatte eventuelle dyr, som er testet ved samme dosisniveau i forundersøgelsen.
The 5 animals in each main study group will include any animal tested at that dose level in the sighting study
Tilordnes GHS kategori
Classify GHS Category
For disse stoffer forventes en oral eller dermal LD50 i området 2000-5000 mg/kg, eller tilsvarende doser for andre administrationsveje, I følgende tilfælde kan et teststof klassificeres i farekategorien defineret ved: 2000 mg/kg < LD50 < 5000 mg/kg (kategori 5 i GHS):
These substances are anticipated to have an oral or dermal LD50 in the range of 2000-5000 mg/kg or equivalent doses for other routes. Test substances could be classified in the hazard category defined by: 2000 mg/kg < LD50 < 5000 mg/kg (Category 5 in the GHS) in the following cases:
Reglerne i bilag 2 for anvendelse af den sekventielle metode udvides til at omfatte dosisniveauet 5000 mg/kg, Når startdosis i forundersøgelsen er 5000 mg/kg, vil udfald A (≥ 2 dødsfald) kræve testning af endnu en gruppe ved 2000 mg/kg; udfald B (synlig toksicitet og/eller ≤ 1 dødsfald) eller C (ingen toksicitet) vil medføre, at stoffet ikke skal klassificeres i henhold til GHS.
The decision rules governing the sequential procedure presented in Appendix 2 are extended to include a 5000 mg/kg dose level. Thus, when a main study starting dose of 5000 mg/kg is used, outcome A (≥ 2 deaths) will require the testing of a second group at 2000 mg/kg; outcome B (evident toxicity and/or ≤ 1 death) or C (no toxicity) will result in the substance being unclassified according to GHS.
U = Ingen klassificering
U + unclassified
Akut toksicitetsklassemetoden bygger på biometriske vurderinger (2)(3)(4)(5) med faste doser, der er spredt således, at et stofs giftighed kan bestemmes med henblik på klassificering og risikovurdering, Metoden blev indført i 1996 og er blevet grundigt valideret in vivo over for LD50-data fra litteraturen, både nationalt (6) og internationalt (7).
The acute toxic class method is based on biometric evaluations (2)(3)(4)(5) with fixed doses, adequately separated to enable a substance to be ranked for classification purposes and hazard assessment. The method as adopted in 1996 was extensively validated in vivo against LD50 data obtained from the literature, both nationally (6) and internationally (7).
Moribund tilstand: en tilstand, hvor dyret er døende eller ikke vil overleve, selv om det behandles (se nærmere i Humane Endpoint Guidance Document (9)).
Moribund status: being in a state of dying or inability to survive, even if treated (See the Humane Endpoint Guidance Document (9) for more details).
Forudsigelig død: tilstedeværelse af kliniske tegn.
Predictable death: presence of clinical signs indicative of death at a known time in the future before the planned end of the experiment; for example: inability to reach water or food.
Efter fasteperioden vejes dyrene, og teststoffet indgives, Når stoffet er indgivet, kan dyrene unddrages føde i yderligere 3-4 timer for rotter og 1-2 timer for mus.
Following the period of fasting, the animals should be weighed and the test substance administered. After the substance has been administered, food may be withheld for a further three or fours hours in rats or one or two hours in mice.
Undtagelsesvis, og kun når det kan begrundes konkret ud fra myndighedsregler, kan det overvejes at anvende et supplerende højeste fast dosisniveau på 5000 mg/kg (se bilag 2), Af dyrevelfærdsmæssige grunde anbefales det at undgå testning i området svarende til GHS-kategori 5 (2000-5000 mg/kg), som kun bør overvejes, når resultaterne af et sådant forsøg med overvejende sandsynlighed ventes at få direkte relevans for beskyttelsen af dyrs eller menneskers sundhed eller miljøet.
Exceptionally, and only when justified by specific regulatory needs, the use of additional upper dose level of 5000 mg/kg body weight may be considered (see Appendix 2). For reasons of animal welfare concern, testing of animals in GHS Category 5 ranges (2000-5000 mg/kg) is discouraged and should only be considered when there is a strong likelihood that the results of such a test would have a direct relevance for protecting human or animal health or the environment.
Viser dyrene fortsat tegn på toksicitet, vil supplerende observationer være nødvendige, Observationerne skal omfatte forandringer i hud, pels, øjne og slimhinder, respirationssystem, kredsløb, autonome nervesystem og centralnervesystem, samt somatomotorisk aktivitet og adfærdsmønster.
Additional observations will be necessary if the animals continue to display signs of toxicity. Observations should include changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour pattern.
Raven Press, Ltd, New York, USA.
Raven Press, Ltd., New York, USA.
For hver startdosis er anvist korrekt fremgangsmåde i den pågældende forsøgsplan i dette bilag.
For each starting dose, the respective testing schemes as included in this Appendix outline the procedure to be followed.
Bilag 1 A: Startdosis er 5 mg/kg kropsvægt
Appendix 1 a: starting dose is 5 mg/kg bw,
Bilag 1 B: Startdosis er 50 mg/kg kropsvægt
Appendix 1 b: starting dose is 50 mg/kg bw,
Bilag 1 C: Startdosis er 300 mg/kg kropsvægt
Appendix 1 c: starting dose is: 300 mg/kg bw,
Bilag 1 D: Startdosis er 2000 mg/kg kropsvægt
Apendix 1 d: starting dose is: 2000 mg/kg bw.
Ved forsøgsgangen følges pilene, afhængigt af antallet af humant aflivede eller døde dyr.
Depending on the number of humanely killed or dead animals, the test procedure follows the indicated arrows.
FREMGANGSMÅDE VED ANVENDELSE AF EN STARTDOSIS PÅ 5 MG/KG KROPSV ÆGT
TEST PROCEDURE WITH A STARTING DOSE OF 5 MG/KG BODY WEIGHT
Afgrænset ved LD50 mg/kg b. w.
cut-off mg/kg b.w.
på hvert trin anvendes 3 dyr af samme køn (normalt hunner)
per step 3 animals of a single sex (normally females) are used
FREMGANGSMÅDE VED EN STARTDOSIS PÅ 50 MG/KG KROPSVÆGT
TEST PROCEDURE WITH A STARTING DOSE OF 50 MG/KG BODY WEIGHT
på hvert trin anvendes 3 dyr af samme køn (normalt hunner)
0, 1, 2, 3: Number of moribund or dead animals at each step - GHS: Globally Harmonised Classification System (mg/kg b.w.) - ∞: unclassified
GHS: Globally Harmonised Classification System (mg/kg b.w.)
Appendix 1D TEST PROCEDURE WITH A STARTING DOSE OF 2000 MG/KG BODY WEIGHT Start 5 mg/kg 3 animals 50 mg/kg 3 animals
Ingen klassificering
300 mg/kg 3 animals 2000 mg/kg 3 animals 5 mg/kg 3 animals 50 mg/kg 3 animals
Testning ved 5000 mg/kg: se bilag 2
300 mg/kg 3 animals 2000 mg/kg 3 animals GHS Category 1 > 0 - 5 Category 2 > 5 - 50 Category 3 > 50 - 300 Category 4 > 300 - 2000 Category 5 > 2000 - 5000 ∞ 3 (at 50) at 1st step other 3 (at 300) at 1st step other
KRITERIER FOR KLASSIFICERING AF TESTSTOFFER MED FORVENTET LD50 OVER 2000 MG/KG UDENAT TESTNING ER NØDVENDIG
Testing at 5000 mg/kg b.w.: see Appendix 2 -------------------------------------------------- Appendix 2
Kriterierne for farekategori 5 skal gøre det muligt at udpege teststoffer, som udviser relativ lav risiko for akut giftighed, men som under visse omstændigheder kan udgøre en fare for følsomme populationer.
CRITERIA FOR CLASSIFICATION OF TEST SUBSTANCES WITH EXPECTED LD50 VALUES EXCEEDING 2000 MG/KG WITHOUT THE NEED FOR TESTING Criteria for hazard Category 5 are intended to enable the identification of test substances which are of relatively low acute toxicity hazard but which, under certain circumstances may present a danger to vulnerable populations.
For disse stoffer forventes en oral eller dermal LD50 i området 2000-5000 mg/kg, eller tilsvarende doser for andre administrationsveje. i følgende tilfælde skal et teststof klassificeres i farekategorien defineret ved: 2000 mg/kg < LD50 < 5000 mg/kg (kategori 5 i GHS):
These substances are anticipated to have an oral or dermal LD50 in the range of 2000-5000 mg/kg or equivalent doses for other routes. The test substance should be classified in the hazard category defined by: 2000 mg/kg < LD50 < 5000 mg/kg (Category 5 in the GHS) in the following cases:
US EPA erk
US EPA crk
Det kan være nødvendigt, at dyr, der viser vedvarende symptomer på stærk smerte eller lidelse, aflives på human måde.
Animals showing severe and enduring signs of distress and pain may need to be humanely killed.
Undersøgelse af stoffer på en måde, som på grund af deres ætsende eller lokalirriterende egenskaber vides at volde betydelig smerte og lidelse, er ikke påkrævet.
Dosing test substances in a way known to cause marked pain and distress due to corrosive or severe irritating properties need not be carried out.
Observationsperiodens varighed bør dog ikke fastsættes rigoristisk, men bestemmes ud fra de toksiske reaktioner, hvornår disse indtræder, og restitutionsperiodens længde; den kan således forlænges, såfremt det anses for nødvendigt.
However, the duration of observations should not be rigidly fixed. It should be determined by the toxic reactions, their rate of onset and the length of the recovery period; it may thus be extended when considered necessary.
Aflivning af dyr på human måde på grund af lidelse og smerte fremkaldt af teststoffet registreres som teststofrelaterede dødsfald, LC50 bestemmes efter en anerkendt metode.
Animals, which are humanely killed due to compound-related distress and pain are recorded as compound-related deaths. The LC50 should be determined by a recognised method.
Undersøgelse af stoffer på en måde, som på grund af deres ætsende eller lokalirriterende egenskaber vides at volde betydelig smerte og lidelse, er ikke påkrævet.
Dosing test substances in a way known to cause marked pain and distress due to corrosive or irritating properties need not be carried out.
Der anvendes mindst fem dyr (af samme køn) til hvert dosisniveau.
At least five animals are used at each dose level. They should all be of the same sex.
Observationsperiodens varighed bør dog ikke fastsættes rigoristisk, men bestemmes ud fra de toksiske reaktioner, hvornår disse indtræder, og af restitutionsperiodens længde; den kan således forlænges, såfremt det anses for nødvendigt.
However, the duration of observation should not be rigidly fixed. It should be determined by the toxic reactions, their rate of onset and the length of the recovery period; it may thus be extended when considered necessary.
Der foretages systematiske observationer, som registreres for hvert enkelt dyr.
Observations should be recorded systematically as they are made. Individual records should be maintained for each animal.
bestemmes efter en anerkendt metode.
The LD50 should be determined by a recognised method.
INDLEDNING
INTRODUCTION In the preparation of this updated method special attention was given to possible improvements in relation to animal welfare concerns and to the evaluation of all existing information on the test substance in order to avoid unnecessary testing in laboratory animals. This method includes the recommendation that prior to undertaking the described in vivo test for corrosion/irritation of the substance, a weight-of-the-evidence analysis be performed on the existing relevant data.
Sådanne data består af dokumentation fra foreliggende undersøgelser i mennesker og/eller laboratoriedyr, dokumentation for ætsende/irriterende virkning af et eller flere strukturelt beslægtede stoffer eller af blandinger af sådanne stoffer, data, som viser at stoffet er stærkt surt eller alkalisk (2)(3), og resultater af validerede og anerkendte in vitro- eller ex vivo-test (4)(5)(5a).
Such data will include evidence from existing studies in humans and/or laboratory animals, evidence of corrosivity/irritation of one or more structurally related substances or mixtures of such substances, data demonstrating strong acidity or alkalinity of the substance (2)(3), and results from validated and accepted in vitro or ex vivo tests (4)(5)(5a). This analysis should decrease the need for in vivo testing for dermal corrosivity/irritation of substances for which sufficient evidence already exists from other studies as to those two endpoints.
Skønt sekventiel testning ikke indgår som en del af testmetode B.4, anbefales det at følge denne testningsstrategi før iværksættelse af in vivo-forsøg, For nye stoffer anbefales den trinvise testningsstrategi til at indhente videnskabeligt forsvarlige oplysninger om stoffets ætsende/irriterende virkning.
It is recommended that this testing strategy be followed prior to undertaking in vivo testing. For new substances it is the recommended a stepwise testing approach for developing scientifically sound data on the corrosivity/irritation of the substance.
Graden af irritation/ætsning bestemmes og klassificeres med de foreskrevne intervaller og beskrives yderligere, således at virkningerne evalueres komplet.
The degree of irritation/corrosion is read and scored at specified intervals and is further described in order to provide a complete evaluation of the effects. The duration of the study should be sufficient to evaluate the reversibility or irreversibility of the effects observed.
Temperaturen i forsøgslokalet skal være 20 oC (± 3 oC) for kaniner.
The temperature of the experimental animal room should be 20 oC (± 3 oC) for rabbits.
Den relative luftfugtighed skal være mindst 30 % og helst ikke være over 70 %, hvilket dog ikke gælder under rengøring af lokalet, men 50-60 % bør tilstræbes.
Although the relative humidity should be at least 30 % and preferably not exceed 70 %, other than during room cleaning, the aim should be 50-60 %.
Guidance Document on the Recognition. Assessment and Use of Clinical Signs as Humane Endpoints for Experimental Animals Used in Safety Evaluation.
Guidance Document on the Recognition, Assessment and Use of Clinical Signs as Humane Endpoints for Experimental Animals Used in Safety Evaluation.
Atlas of Dermal Lesions, (20T-2004). United States Environmental Protection Agency, Office of Pesticides and Toxic Substances.
Atlas of Dermal Lesions, (20T-2004).
Washington, DC, august 1990.
United States Environmental Protection Agency, Office of Pesticides and Toxic Substances, Washington, DC, August 1990.
[kan rekvireres fra OECD's sekretariat].
[Available from OECD Secretariat upon request].
Det kan tænkes, at der allerede foreligger tilstrækkelige vidnesbyrd til, at teststoffets hudætsende eller irriterende potentiale kan klassificeres uden laboratorieforsøg i dyr, Ved hjælp af weight-of-the-evidence-analyse og en sekventiel testningsstrategi kan behovet for in vivo-testning således nedsættes til et minimum, navnlig når stoffet forventes at fremkalde svære reaktioner.
Sufficient evidence may already exist to classify a test substance as to its dermal corrosion or irritation potential without the need to conduct testing in laboratory animals. Therefore, utilising a weight-of-the-evidence analysis and a sequential testing strategy, will minimise the need for in vivo testing, especially if the substance is likely to produce severe reactions.
Strategien tilvejebringer en metode til evaluering af foreliggende oplysninger om teststoffets hudirriterende og ætsende egenskaber og en trinvis fremgangsmåde til at generere relevante data om stoffer, som har behov for yderligere undersøgelse eller ikke er blevet undersøgt, Den giver desuden anbefalinger før udførelse af validerede og anerkendte in vitro- eller ex vivo-test for hudætsning/irritation under nærmere bestemte forhold.
The strategy provides an approach for the evaluation of existing data on the skin irritation/corrosion properties of test substances and a tiered approach for the generation of relevant data on substances for which additional studies are needed, or for which no studies have been performed. It also recommends the performance of validated and accepted in vitro or ex vivo tests for skin corrosion/irritation under specific circumstances.
Primært må de foreliggende data om stoffets virkning på dyr og mennesker tillægges vægt, efterfulgt af resultaterne af in vitro- eller ex vivo-testning, Når det på nogen måde er muligt, bør in vivo-undersøgelser af ætsende stoffer undgås.
Primary emphasis should be placed upon existing human and animal data on the substance, followed by the outcome of in vitro or ex vivo testing. In vivo studies of corrosive substances should be avoided whenever possible.
Endvidere kan den form, hvori teststoffet er tilført dyrene, have være uegnet til vurdering af hudirritation/ætsning (f.eks stoffets fortynding ved undersøgelse af hudtoksicitet (5)), I de tilfælde, hvor der foreligger veldesignede og veludførte hudtoksicitetsundersøgelser i kaniner, kan negative fund anses som tilstrækkelig dokumentation for, at stoffet ikke er ætsende eller irriterende.
Also the form of test substance applied to animals may not have been suitable for assessment of skin irritation/corrosion (e.g., dilution of substances for testing dermal toxicity (5). However, in those cases in which well-designed and conducted dermal toxicity studies have been performed in rabbits, negative findings may be considered sufficient evidence that the substance is not corrosive or irritating.
OECD (1996), Test Guidelines Programme: Final Report on the OECD Workshop on Harmonisation of Validation and Acceptance Criteria for Alternative Toxicological Test Methods, afholdt i Solna, Sverige, den 22.-24. januar 1996 (http://www.1.oecd.org/ehs/test/background.htm).
OECD, (1996) Test Guidelines Programme: Final Report on the OECD Workshop on Harmonisation of Validation and Acceptance Criteria for Alternative Toxicological Test Methods. Held on Solna, Sweden, 22-24 January 1996 (http://www1.oecd.org/ehs/test/background.htm).
Classification as Corrosive or Irritant to Skin of Preparations Containing Acidic or Alkaline Substances, Without Testing on Animals.
Classification as Corrosive or Irritant to Skin of Preparations Containing Acidic or Alkaline Substances, Without Testing on Animals.
I metoden indgår en anbefaling om, at der før iværksættelse af den beskrevne in vivo-test for akut øjenirritation/ætsning udføres en weight-of-the-evidence-analyse (1) af foreliggende relevante data, Er de foreliggende data utilstrækkelige, anbefales det, at de suppleres ved sekventiel testning (2)(3).
This method includes the recommendation that prior to undertaking the described in vivo test for acute eye irritation/corrosion, a weight-of-the-evidence analysis be performed (1) on the existing relevant data. Where insufficient data are available, it is recommended that they be developed through application of sequential testing (2)(3).
Den anbefalede testningsstrategi, som omfatter validerede og anerkendte in vitro-test, er givet som bilag til denne metodebeskrivelse, Derudover anbefales det at udføre en in vivo-test for hudirritation/ætsning med henblik på at kunne forudsige ætsning af øjet, før en in vivo-øjentest overvejes gennemført.
The testing strategy includes the performance of validated and accepted in vitro tests and is provided as an Appendix to the testing method. In addition, the use of an in vivo dermal irritation/corrosion test to predict eye corrosion prior to consideration of an in vivo eye test is recommended. In the interest of both sound science and animal welfare, in vivo testing should not be considered until all available data relevant to the potential eye corrosivity/irritation of the substance has been evaluated in a weight-of-the-evidence analysis.
Både den videnskabelige kvalitet og dyrenes velfærd fremmes ved, at in vivo-test ikke udføres, før alle relevante data om stoffets potentielle øjenætsende eller -irriterende egenskaber er vurderet ved weight-of-the-evidence-analyse, Sådanne data består af dokumentation fra foreliggende undersøgelser i mennesker og/eller laboratoriedyr, dokumentation for ætsende/irriterende virkning af et eller flere strukturelt beslægtede stoffer eller af blandinger af sådanne stoffer, data, som viser at stoffet er stærkt surt eller alkalisk (4)(5), og resultater af validerede og anerkendte in vitro- eller ex vivo-test for hudætsning og -irritation (6)(6a).
Such data will include evidence from existing studies in humans and/or laboratory animals, evidence of corrosivity/irritation of one or more structurally related substances or mixtures of such substances, data demonstrating high acidity or alkalinity of the substance (4)(5), and results from validated and accepted in vitro or ex vivo tests for skin corrosion and irritation (6)(6a). The studies may have been conducted prior to, or as a result of, a weight-of-the-evidence analysis.
Skønt sekventiel testning ikke indgår som en del af testmetode B.4, anbefales det at følge denne testningsstrategi, før in vivo-forsøg iværksættes, For nye stoffer anbefales den trinvise testningsstrategi til at indhente videnskabeligt forsvarlige oplysninger om stoffets ætsende/irriterende virkning.
It is recommended that this testing strategy be followed prior to undertaking in vivo testing. For new substances it is the recommended stepwise testing approach for developing scientifically sound data on the corrosivity/irritation of the substance.