PLATELIA™ TOXO IgG AVIDITY 48 72842 DETERMINATION OF ANTI-TOXOPLASMA GONDII IgG AVIDITY IN HUMAN SERUM BY ENZYME IMMUNOASSAY

881130 - 2013/11 Table of Content

1- INTENDED USE...... 3

2- CLINICAL VALUE...... 3

3- PRINCIPLE...... 4

4- PRODUCT INFORMATION...... 5

5- WARNINGS AND PRECAUTIONS...... 5

6- SAMPLES...... 7

7- ASSAY PROCEDURE...... 7

8- INTERPRETATION OF RESULTS...... 10

9- PERFORMANCES...... 11

10- LIMITATIONS OF THE PROCEDURE...... 13

11- QUALITY CONTROL OF THE MANUFACTURER...... 13

12- REFERENCES...... 14

2 [EN] 1. INTENDED USE Platelia™ TOXO IgG AVIDITY is an immuno-enzyme assay for determination of avidity of anti-T. gondii IgG antibodies in human serum. The Platelia™ TOXO IgG AVIDITY assay should be used in association with the Platelia™ TOXO IgG kit (Ref. 72840). 2. CLINICAL VALUE T. gondii is a protozoan causing infection in numerous species of mammals and birds. Toxoplasmosis, frequent in humans and animals, are more typically silent. The prevalence of this infection in the population, established using serological tests, may differ depending upon the country of origin and the age. Toxoplasmosis during pregnancy has been implicated in serious congenital abnormalities (in particular, impaired brain functions) and sometimes stillbirth. Demonstration of Toxo IgG antibody in women prior to conception provides assurance of fetal protection from possible toxoplasmosis during pregnancy. Predisposition to severe toxoplasmosis infection is common in persons known to have Acquired Immune Deficiency Syndrome (AIDS), or who are otherwise immunocompromised. These infections are mainly due to reactivation of T. gondii cysts present prior to the HIV infection. Specific diagnosis of T. gondii infection can be complicated and isolation of the parasite is rare. Serologic confirmation ofT. gondii antibody is indicative of exposure to the parasite and has become widely accepted as a means to determine immune status and susceptibility to infection. Screening of several isotypes allows either the dating of the T. gondii and the implementation of appropriate therapy in case of recent infection or the proposal of prophylactic recommendations: hygiene-diet guidelines in pregnant women, chemo- prophylaxy in immunocompromised population. However, differential diagnosis between recent and past-infection is sometimes difficult due to persistence of anti-T. gondii IgM antibodies or re-apparition of anti-T. gondii IgM in case of re-infection, reactivation of a latent infection or non specific stimulation of the immune system. In such situations, IgG avidity measurement by an immuno-enzyme method can help to differentiate between acute or past-infection. This determination is based on evolution of the immune response maturity, which translates in synthesis of low avidity IgG antibodies during primo-infections and of high avidity IgG antibodies during past-infections.

3 [EN] 3. PRINCIPLE This test is carried out using Platelia™ TOXO IgG AVIDITY (Ref. 72842) in association with Platelia™ TOXO IgG (Ref. 72840). The principle of this method relies on the measurement of the avidity of the IgG antibodies to T. gondii. The use of an agent (as urea) dissociating the link antigen/antibody in parallel with the usual technique of IgG antibodies measurement allows comparison of the optical density (OD) obtained after dissociating agent action and OD obtained without dissociating agent action. The avidity is considered low when the antigen/antibody link is easily dissociated. The avidity is considered high when the antigen/antibody link is not easily dissociated. This test has to be used only on positive samples that demonstrate an anti-T. gondii IgG concentration higher or equal to 9 IU/ml with Platelia™ TOXO IgG (Ref. 72840). • Step 1 Avidity controls and patient sera with a concentration of anti-T. gondii IgG between 9 and 80 IU/ml are diluted to 1/101. Sera from patients with a concentration of anti-T. gondii IgG equal or higher than 80 IU/ml are diluted to 1/808. Diluted samples are then distributed twice into T. gondii antigen coated wells of the microplate. During this incubation of one hour at 37°C, IgG antibodies to T. gondii present in the sample bind to the T. gondii antigen coated on microplate wells. After incubation, unbound non specific antibodies and other serum proteins are removed by washings. • Step 2 Each avidity control and each patient serum is treated in double: control solution is added in one well and dissociating solution in the other well. During this incubation of 15 minutes at room temperature (+18-30°C), the dissociating solution tries to dissociate the antigen/antibody complexes. After incubation, both solutions and dissociated IgG are removed by washings. • Step 3 The conjugate (peroxydase labeled polyclonal antibody specific for human gamma chains) is added to the microplate wells. During this incubation of one hour at 37°C, the labeled antibody binds to the serum IgG captured by the T. gondii antigen. The unbound conjugate is removed by washings at the end of the incubation. • Step 4 The presence of immune-complexes (T. gondii antigen, IgG antibodies to T. gondii, anti-IgG conjugate) is demonstrated by the addition in each well of an enzymatic development solution.

4 [EN] • Step 5 After incubation of 30 minutes at room temperature (+18-30°C), the enzymatic reaction is stopped by addition of 1N sulfuric acid solution. The optical density reading obtained with a spectrophotometer set at 450/620 nm is proportional to the amount of IgG antibodies to T. gondii present in the well. 4. PRODUCT INFORMATION Supplied quantities of reagents have been calculated to allow 48 tests with the Platelia™ TOXO IgG kit (Ref. 72840). All reagents are exclusively for in vitro diagnostic use.

Label Nature of reagents Presentation R5a Low Avidity Low Avidity Control: 1 x 0.75 mL Control Human serum reactive for IgG antibodies to T. gondii, and negative for HBs antigen, anti- HIV1, anti-HIV2 and anti-HCV Preservative : 0.15% ProClin™ 300 R5b High Avidity High Avidity Control: 1 x 0.75 mL Control Human serum reactive for IgG antibodies to T. gondii, and negative for HBs antigen, anti- HIV1, anti-HIV2 and anti-HCV Preservative : 0.15% ProClin™ 300 R12 Control Control Solution: 1 x 28 mL Solution TRIS-NaCl buffer (pH 7.6 ± 0.2), 0.1% Tween® 20 and green dye Preservative : 0.15% ProClin™ 300 R13 Dissociating Dissociating Solution: 1 x 13 mL Solution TRIS-NaCl buffer (pH 7.6 ± 0.2), urea, 0.1% Tween® 20 et yellow dye Preservative : 0.001% ProClin™ 300

For storage conditions and expiration date, please refer to the indications stated on the box. 5. WARNINGS AND PRECAUTIONS The reliability of the results depends on correct implementation of the following Good Laboratory Practices: • Do not use expired reagents. • Do not mix or associate within a given run reagents from different lots. • Before use, wait for 1H30 minutes to allow reagents to reach room temperature (+18-30°C).

5 [EN] • Use glassware thoroughly washed and rinsed with deionized water or, preferably disposable material. • Use a new pipette tip for each sample. • Check the pipettes and other equipments for accuracy and correct operations. • Strictly follow the assay procedure. • Refer also to the Platelia™ TOXO IgG product insert (Ref. 72840). Note: Platelia™ TOXO IgG AVIDITY kit can be used with different lots of Platelia™ TOXO IgG (Ref. 72840).

HEALTH AND SAFETY INSTRUCTIONS Human origin material used in the preparation of reagents has been tested and found non-reactive for hepatitis B surface antigen (HBs Ag), antibodies for hepatitis C virus (anti-HCV), and to human immunodeficiency virus (anti-HIV1 and anti-HIV2). Because no method can absolutely guarantee the absence of infectious agents, handle reagents of human origin and patient samples as potentially capable of transmitting infectious diseases: • Any material, including washings solutions, that comes directly in contact with samples and reagents containing materials of human origin should be considered capable of transmitting infectious diseases. • Wear disposable gloves when handling samples and reagents. • Do not pipette by mouth. • Avoid spilling samples or solutions containing samples. Spills must be rinsed with bleach diluted to 10 %. In the event of a spill with an acid, it must be first neutralized with sodium bicarbonate, and then cleaned with bleach diluted to 10% and dried with adsorbent paper. The material used for cleaning must be discarded in a contaminated residue container. • Patient samples, reagents containing human origin material, as well as contaminated material and products should be discarded after deconta- mination only. • Chemical and biological residues must be handled and disposed off in accordance with Good Laboratories Practices. • All reagents in the kit are exclusively for in vitro diagnostic use. • For hazard and precaution recommendations related to some chemical components in this test kit, please refer to the pictogram(s) mentioned on the labels and the information supplied at the end of instruction for use. The Safety Data Sheet is available on www.bio-rad.com.

6 [EN] 6. SAMPLES 1. Serum is the only recommended sample type. 2. Observe the following recommendations for handling, processing and storage of blood samples: • Collect all blood samples observing routine precaution for venipuncture. • Allow samples to clot completely before centrifugation. • Keep tubes stoppered at all times. • After centrifugation, separate the serum from the clot or red cells in a tightly stoppered storage tube. • The specimens can be stored at +2-8°C if test is performed within 7 days. • If test will not be completed within 7 days, or for shipment, freeze the samples at -20°C or colder. • Do not use samples that have been thawed more than five times. Previously frozen specimens should be thoroughly mixed (Vortex) after thawing prior to testing. 3. Samples containing 90 g/l of albumin or 100 mg/l of unconjugated bilirubin, lipemic samples containing the equivalent of 36 g/l of triolein (triglyceride), and hemolysed samples containing up to 10 g/l of hemoglobin do not affect the results. 4. Do not heat the samples. 7. ASSAY PROCEDURE 7.1 Materials required but not provided Refer to the Platelia™ TOXO IgG product insert (Ref. 72840). 7.2 Reagents reconstitution • R5a, R5b: Low Avidity Control (R5a) and High Avidity Control (R5b) must be diluted to 1/101 using the Diluent R7 supplied within the Platelia™ TOXO IgG assay (Ref. 72840). • R12, R13: Control Solution (R12) and Dissociating Solution (R13) are ready- to-use. • For other reagents, please refer to the Platelia™ TOXO IgG product insert (Ref. 72840). 7.3 Storage and validity of opened and / or reconstituted reagents The kit must be stored at +2-8°C. When the kit is stored at +2-8°C before opening, each component can be used until the expiration date indicated on the outer label of the kit. • R5a, R5b: Once opened and without any contamination, the reagents stored at +2-8°C are stable for up to 16 weeks.

7 [EN] • R12, R13: Once opened and without any contamination, the reagents stored at +2-8°C are stable for up to 16 weeks. Refer also to the Platelia™ TOXO IgG product insert (Ref. 72840). 7.4 Procedure Strictly follow the assay procedure and Good Laboratory Practices. Use Low Avidity (R5a) and High Avidity (R5b) controls with each run to validate the assay results. Other reagents to use (R1, R2, R6, R7, R9 and R10) are included within the Platelia™ TOXO IgG kit (Ref. 72840). Note: before use, wait for 1H30 minutes to allow reagents to reach room temperature (+18-30°C), especially reagents R12 and R13. 1. Carefully establish the distribution and identification plan for controls and patients samples. 2. Prepare the diluted Washing Solution (R2). 3. Take the carrier tray and the strips (R1) out of the protective pouch. 4. In individually identified tubes, dilute to 1/101 in Diluent (R7) the avidity controls (R5a, R5b) and the patient samples (S1, S2…) having anti-T. gondii IgG concentration between 9 and 80 IU/ml [10 µl of sample and 1 ml of Diluent (R7)]. Sera of patients with a concentration of anti-T. gondii IgG equal or higher than 80 IU/ml are diluted to 1/808 [10 µl of sample and 1 ml of Diluent (R7) then 100 µl of the first dilution and 700 µl of Diluent (R7)]. Vortex diluted samples. 5. Strictly following the indicated sequence below, distribute in each well with 200 µl of diluted controls and patient samples:

1 2 3 4 5 6 7 8 9 10 11 12 A R5a R5a S7 S7 B R5b R5b C S1 S1 D S2 S2 E S3 S3 F S4 S4 G S5 S5 H S6 S6

6. Cover the microplate with an adhesive plate sealer, then press firmly onto the plate to ensure a tight seal. Incubate the microplate immediately in a thermostat controlled water bath or in a dry incubator for 1 hour ± 5 minutes at 37°C ± 1°C.

8 [EN] 7. At the end of the first incubation period, remove the adhesive plate sealer. Aspirate the content of all wells into a container for biohazard waste (containing sodium hypochloride). 8. Quickly distribute 200 µl of the Control Solution (R12) in each well of odd strips. Then, quickly distribute 200 µl of the Dissociating Solution (R13) in each well of the even strips. 9. Incubate the microplate for 15 minutes ± 2 min. at room temperature (+18-30°C). 10. Before the end of the incubation period, prepare the conjugate working solution (R6+R7). 11. At the end of the incubation period, aspirate the content of all wells into a container for biohazard waste (containing sodium hypochloride). Wash microplate 2 times with 350 µl of the Washing Solution (R2). Invert the microplate and gently tap on adsorbent paper to remove remaining liquid. 12. Distribute immediately 200 µl of the conjugate working solution (R6+R7) in all wells. The solution must be shaken gently before use. 13. Cover the microplate with an adhesive plate sealer, then press firmly onto the plate to ensure a tight seal. Incubate the microplate immediately in a thermostat controlled water bath or in a dry incubator for 1 hour ± 5 minutes at 37°C ± 1°C. 14. At the end of the incubation period, remove the adhesive plate sealer. Aspirate the content of all wells into a container for biohazard waste (containing sodium hypochloride). Wash microplate 4 times with 350 µl of the Washing Solution (R2). Invert the microplate and gently tap on adsorbent paper to remove remaining liquid. 15. Quickly distribute into each well and away from light 200 µl of Chromogen solution (R9). Allow the reaction to develop in the dark for 30 ± 5 minutes at room temperature (+18-30°C). Do no use adhesive plate sealer during this incubation. 16. Stop the enzymatic reaction by adding 100 µl of Stopping Solution (R10) in each well. Use the same sequence and rate of distribution as for the development solution. 17. Carefully wipe the plate bottom. Read the optical density at 450/620 nm using a plate reader within 30 minutes after stopping the reaction. The strips must always be kept away from light before reading. 18. Before reporting results, check for agreement between the reading and the distribution plan of plate and samples.

9 [EN] 8. INTERPRETATION OF RESULTS 8.1 Calculation of Avidity Index The Avidity Index (AI) of a sample is the ratio of optical densities (OD) measured with the Dissociating Solution (R13) and the Control Solution (R12): AI = ODSample R13 / ODSample R12 Calculation of AI of a sample can be realised only if OD obtained with the Control Solution is higher than 0.150. 8.2 Quality Control Include all the controls for each microplate and for each run, and analyze the obtained results. For validation of the assay, the following criteria must be met: • Optical density values with the Control Solution (R12): OD R5a ≥ 0.200 OD R5b ≥ 0.200 • Avidity Indexes: AI R5a < 0.40 AI R5b ≥ 0.50 If those quality control criteria are not met, the test run should be repeated. 8.3 Interpretation of results

Avidity Index (AI) Interpretation AI < 0.40 Low avidity zone 0.40 ≤ AI < 0.50 Avidity intermediate zone AI ≥ 0.50 High avidity zone

Avidity indexes lower than 0.40 are more in favor of recent primo-infection of less than 20 weeks. However, such results do not allow confirmation of this diagnosis with absolute certainty. Avidity indexes higher or equal to 0.50 are more in favor of past-infection of more than 20 weeks. However, such results do not allow exclusion of a recent primo-infection of less than 20 weeks with absolute certainty. If a recent infection is suspected or if avidity index is in the grey zone, a second sample can be tested (Refer to the actual legislation regarding patients monitoring).

10 [EN] 8.4 Trouble Shooting Guide Non validated or non repeatable reactions are often caused by: • Inadequate temperature of reagents • Inadequate microplate washings. • Incorrect samples dilution • Contamination of negative samples by serum with a high antibody titer. • Contamination of the development solution by chemical oxidizing agents (bleach, metal ions...). • Contamination of the Stopping Solution. 9. PERFORMANCES 9.1 Clinical studies Performances of Platelia™ TOXO IgG AVIDITY were evaluated in an hospital lab using 297 samples essentially from pregnant women, including 33 samples from seroconversion panels. A prospective study was realized on 72 samples found positive for anti-T.gondii IgG with Platelia™ TOXO IgG (72840). For 65 of them, Platelia™ TOXO IgG AVIDITY results were compared with those obtained using a commercialized EIA IgG avidity assay considered as the reference. Only 9 minor discrepancies have been observed: • 2 samples with low avidity index using the reference test were found of intermediate avidity with Platelia™ TOXO IgG AVIDITY. • 4 samples with intermediate avidity index using the reference test were found of high avidity with Platelia™ TOXO IgG AVIDITY. • 3 samples with high avidity index using the reference test were found of intermediate avidity with Platelia™ TOXO IgG AVIDITY. A retrospective study was performed on 93 samples positive for anti-T. gondii IgG and negative for anti-T. gondii IgM, and considered as past toxo-plasmosis. Among these samples: • 82 presented a high avidity index. • 9 presented an intermediate avidity index • 2 presented a low avidity index The 9 sera showing an intermediate avidity index correspond to adult past- infection and present an avidity index close to the high avidity limit. The 2 sera of low avidity are from cord blood. One of them corresponds to a pregnant women that has been treated after a seroconversion, explaining the IgG maturation delay. For the other sample, no information on the mother’s serological status was available. 99 samples positive for anti-T. gondii IgG and for anti-T. gondii IgM were also tested. The avidity indexes obtained were compared to those obtained with the reference method: 11 [EN] Avidity Reference Test Low Intermediate High avidity Avidity avidity Low avidity 21 0 0 Platelia™ TOXO IgG Intermediate 5** 5 2 Avidity Avidity (72842) High avidity 1* 12 53

Among the observed discrepancies: • After retest with both assays, a minor discrepancy was confirmed for one sample(*). It corresponds to a woman whose toxoplasmosis was older than 2 months before sampling. • One sample(**) from a seroconversion and presenting a minor discrepancy gave a low avidity index with both assays after retest. • 10 samples were not controlled as they corresponded to past infection and presented minor discrepancies. All these samples demonstrated an intermediate avidity index close from the high avidity threshold with the reference test and a high avidity index with Platelia™ TOXO IgG AVIDITY. • For 6 of the 8 remaining samples, a minor discrepancy remains after retest (high avidity vs intermediate ; intermediate vs high ; low vs intermediate) 33 samples from toxoplasmosis seroconversions of less than 2 months were also tested. These sera corresponded to the first anti-T. gondii IgG positive sample and were all of low avidity index with Platelia™ TOXO IgG AVIDITY. 9.2 Precision Precision studies were realized on 3 anti-T. gondii IgG positive samples diluted to 1/101 and 3 anti-T. gondii IgG positive samples diluted to 1/808. • Within-run precision (repeatability): In order to evaluate intra-assay repeatability, the six samples were tested 30 times during the same run. The avidity indexes were determined for each sample. Mean AI, Standard Deviation (SD) and Coefficient of Variation (%CV) for each sample are listed in the table below: Within-run precision (repeatability)

Low AI Intermediate High AI Low AI Intermediate High AI N=30 1/101 AI 1/101 1/101 1/808 AI 1/808 1/808 Mean 0.14 0.41 0.59 0.20 0.37 0.54 SD 0.01 0.02 0.03 0.01 0.03 0.03 % CV 8.5% 4.1% 5.4% 5.9% 8.0% 5.7%

12 [EN] • Between-run precision (reproducibility): In order to evaluate inter-assay reproducibility, the six samples were tested in duplicate in two runs per day over a 20 days period. The avidity indexes were determined for each sample. Mean AI, Standard Deviation (SD) and Coefficient of Variation (%CV) for each sample are listed in the table below: Between-run precision (reproducibility)

Low AI Intermediate High AI Low AI Intermediate High AI N=80 1/101 AI 1/101 1/101 1/808 AI 1/808 1/808 Mean 0.19 0.42 0.61 0.20 0.42 0.80 SD 0.01 0.02 0.04 0.02 0.03 0.03 % CV 7.5% 5.3% 5.8% 7.9% 7.2% 3.3%

10. LIMITATIONS OF THE PROCEDURE Diagnosis of T. gondii infection can only be established on the basis of a combination of clinical and biological data. The result of a single test of titration of anti-T. gondii IgG antibodies and measurement of their avidity does not constitute sufficient proof for the diagnosis of a recent infection by T. gondii. 11. QUALITY CONTROL OF THE MANUFACTURER All manufactured reagents are prepared according to our Quality System, starting from reception of raw material to commercialization of the final product. Each lot is submitted to quality control assessments and is released to the market only after conforming to pre-defined acceptance criteria. The records related to production and controls of each single lot are kept within Bio-Rad.

13 [EN] 12. REFERENCES 1. COZON, G. J., J. FERRANDIZ, H. NEBHI, M. WALLON, and F. PEYRON. 1998. Estimation of the avidity of immunoglobulin G for routine diagnosis of chronic Toxoplasma gondii infection in pregnant women. Eur.J.Clin. Microbiol.Infect.Dis. 17:32-36. 2. JENUM, P. A., B. STRAY-PEDERSEN, and A. G. GUNDERSEN. 1997. Improved diagnosis of primary Toxoplasma gondii infection in early pregnancy by determination of anti-toxoplasma immunoglobulin G avidity. J.Clin.Microbiol. 35:1972-1977. 3. LAPPALAINEN, M., P. KOSKELA, M. KOSKINIEMI, P. AMMALA, V. HIILESMAA, K. TERAMO, K. O. RAIVIO, J. S. REMINGTON, and K. HEDMAN. 1993. Toxoplasmosis acquired during pregnancy: improved serodiagnosis based on avidity of IgG. J.Infect.Dis. 167:691-697. 4. LECOLIER, B. and B. PUCHEU. 1993. [Value of the study of IgG avidity for the diagnosis of toxoplasmosis]. Pathol.Biol.(Paris) 41:155-158. 5. LECOLIER, B. and B. PUCHEU. 1994. Comparaison de deux techniques de mesure de l’avidité des IgG pour le diagnostic de la toxoplasmose. Rev. Fr.Lab. 274:15-18. 6. REMINGTON J. S., THULLIEZ P., MONTOYA J. G. 2004. Recent Developments for Diagnosis of Toxoplasmosis. J.Clin.Microbiol. 42: 941- 945. 7. ZOTTI, C., L. CHARRIER, M. GIACOMUZZI, R. A. MOIRAGHI, M. MOMBRO, C. FABRIS, and coll. 2004. Use of IgG Avidity test in case definitions of Toxoplasmosis in pregnancy. Microbiologica. 27: 17-20.

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Изхвърлете съдържанието/ EN CASO DE CONTACTO CON LA PIEL: Lavar контейнера в съответствие с местните/ con agua y jabón abundantes. En caso de irritación регионалните/националните/международните o erupción cutánea: Consultar a un médico. разпоредби. Eliminar el contenido o el recipiente conforme a la reglamentación local/regional/nacional/internacional. (CZ) Varování (FI) Může vyvolat alergickou kožní reakci. Varoitus Používejte ochranné rukavice/ochranný oděv/ Voi aiheuttaa allergisen ihoreaktion. ochranné brýle/obličejový štít. PŘI STYKU S Käytä suojakäsineitä/suojavaatetusta/ KŮŽÍ: Omyjte velkým množstvím vody a mýdla. Při silmiensuojainta/kasvonsuojainta. JOS KEMIKAALIA podráždění kůže nebo vyrážce: Vyhledejte lékařskou JOUTUU IHOLLE: Pese runsaalla vedellä ja pomoc/ošetření. Obsah/nádobu likvidujte v souladu saippualla. Jos ilmenee ihoärsytystä tai ihottumaa: s místními/regionálními/národními/mezinárodními Hakeudu lääkäriin. Säilytä säiliö(t) noudattaen předpisy. paikallisia/alueellisia/kansallisia/kansainvälisiä määräyksiä. (DE) Achtung (FR) Kann allergische Hautreaktionen verursachen. Attention Schutzhandschuhe/Schutzkleidung/Augenschutz/ Peut provoquer une allergie cutanée. Gesichtsschutz tragen. BEI KONTAKT MIT DER Porter des gants de protection/des vêtements HAUT: Mit viel Wasser und Seife waschen. Bei de protection/un équipement de protection des Hautreizung oder -ausschlag: Ärztlichen Rat yeux/du visage. EN CAS DE CONTACT AVEC einholen/ärztliche Hilfe hinzuziehen. Entsorgung LA PEAU: laver abondamment à l’eau et au des Inhalts / des Behälters gemäß den örtlichen / savon. En cas d’irritation ou d’éruption cutanée: regionalen / nationalen/ internationalen Vorschriften. consulter un médecin. Éliminer le contenu/récipient conformément à la réglementation locale/régionale/ (DK) nationale/internationale. Advarsel Kan forårsage allergisk hudreaktion. (GR) Bær beskyttelseshandsker/beskyttelsestøj/ Προσοχή øjenbeskyttelse/ansigtsbeskyttelse VED KONTAKT Μπορεί να προκαλέσει αλλεργική δερματική MED HUDEN: Vask med rigeligt sæbe og vand. αντίδραση. Ved hudirritation eller udslet: Søg lægehjælp. Να φοράτε προστατευτικά γάντια/προστατευτικά Bortskaffelse af indholdet/beholderen i henhold til de ενδύματα/μέσα ατομικής προστασίας για ταμάτια/ lokale/regionale/nationale/internationale forskrifter. πρόσωπο. ΣΕ ΠΕΡΙΠΤΩΣΗ ΕΠΑΦΗΣ ΜΕ ΤΟ ΔΕΡΜΑ: Πλύνετε με άφθονο νερό και σαπούνι. Εάν (EE) παρατηρηθεί ερεθισμός του δέρματος ή εμφανιστεί εξάνθημα: Συμβουλευθείτε/Επισκεφθείτεγιατρό. Hoiatus Απορρίψτε τα περιεχόμενα/δοχείο σύμφωνα με τους Võib põhjustada allergilist nahareaktsiooni. τοπικούς/εθνικούς/διεθνείς κανονισμούς. Kanda kaitsekindaid/kaitserõivastust/kaitseprille/ kaitsemaski. NAHALE SATTUMISE KORRAL: pesta rohke vee ja seebiga. Nahaärrituse või _obe (HR) korral: pöörduda arsti poole. Sisu/konteineri käitlus Upozorenje vastavuses kohalike/regionaalsete/rahvuslike/ Može izazvati alergijsku reakciju na koži. rahvusvaheliste nõuetega. Nositi zaštitne rukavice/zaštitnu odijelo/zaštitu za oči/zaštitu za lice. U SLUČAJU DODIRA S KOŽOM: oprati velikom količinom sapuna i vode. U slučaju nadražaja ili osipa na koži: zatražiti savjet/pomoć Stosować rękawice ochronne/odzież ochronną/ liječnika. Odložite sadržaje /spremnike u skladu ochronę oczu/ochronę twarzy. W PRZYPADKU s lokalnim/regionalnim/nacionalni/međunarodnim KONTAKTU ZE SKÓRĄ: Umyć dużą ilością wody odredbama. z mydłem. W przypadku wystąpienia podrażnienia skóry lub wysypki: Zasięgnąć porady/zgłosić się (HU) pod opiekę lekarza. Zawartość / pojemnik usuwać Figyelem zgodnie z przepisami miejscowymi / regionalnymi / narodowymi / międzynarodowymi. Allergiás bőrreakciót válthat ki. Védőkesztyű/védőruha/szemvédő/arcvédő használata kötelező. HA BŐRRE KERÜL: Lemosás (PT) bő szappanos vízzel. Bőrirritáció vagy kiütések Atenção megjelenése esetén: orvosi ellátást kell kérni. Az Pode provocar uma reacção alérgica cutânea. edény tartalmát / a tartályt a helyi/regionális/nemzeti/ Usar luvas de protecção/vestuário de protecção/ nemzetközi szabályozásoknak megfelelően kell protecção ocular/protecção facial. SE ENTRAR EM hulladékként elhelyezni. CONTACTO COM A PELE: lavar com sabonete e água abundantes. Em caso de irritação ou erupção (IT) cutânea: consulte um médico. Eliminar o conteúdo/ Attenzione recipiente de acordo com a legislação local/regional/ nacional/internacional. Può provocare una reazione allergica cutanea. Indossare guanti/indumenti protettivi/Proteggere gli occhi/il viso. IN CASO DI CONTATTO CON LA (RO) PELLE: lavare abbondantemente con acqua e Atenţie sapone. In caso di irritazione o eruzione della pelle: Poate provoca o reacţie alergică a pielii. consultare un medico. Smaltire il prodotto/recipiente Purtaţi mănuşi de protecţie/îmbrăcăminte de in conformità con le disposizioni locali / regionali / protecţie/echipament de protecţie a ochilor/ nazionali / internazionali. chipament de protecţie a feţei. ÎN CAZ DE CONTACT CU PIELEA: spălaţi cu multă apă şi (LT) săpun. În caz de iritare a pielii sau de erupţie Atsargiai cutanată: consultaţi medicul. Aruncaţi conţinutul/ containerul în acord cu regulamentele locale/ Gali sukelti alerginę odos reakciją. regionale/naţionale/internaţionale. Mūvėti apsaugines pirštines/dėvėti apsauginius drabužius/naudoti akių (veido) apsaugos priemones. PATEKUS ANT ODOS: Nuplauti dideliu kiekiu muilo (SE) ir vandens. Jeigu sudirginama oda arba ją išberia: Varning kreiptis į gydytoją. Turinį/talpą išpilti (išmesti) - Kan orsaka allergisk hudreaktion. šalinti pagal vietines / regionines / nacionalines / Använd skyddshandskar/skyddskläder/ögonskydd/ tarptautines taisykles. ansiktsskydd. VID HUDKONTAKT: Tvätta med mycket tvål och vatten. Vid hudirritation eller (NL) utslag: Sök läkarhjälp. Innehållet / behållaren Waarschuwing avfallshanteras enligt lokala / regionala / nationella / internationella föreskrifter. Kan een allergische huidreactie veroorzaken. Beschermende handschoenen/beschermende kleding/oogbescherming/gelaatsbescherming (Sl) dragen. BIJ CONTACT MET DE HUID: met veel Pozor water en zeep wassen. Bij huidirritatie of uitslag: Lahko povzroči alergijski odziv kože. een arts raadplegen. De inhoud en de verpakking Nositi zaščitne rokavice/zaščitno obleko/zaščito za verwerken volgens de plaatselijke/regionale/ oči/zaščito za obraz. PRI STIKU S KOŽO: umiti z nationale/internationale voorschriften. veliko mila in vode. Če nastopi draženje kože ali se pojavi izpuščaj: poiščite zdravniško pomoč/oskrbo. (NO) Vsebino/vsebnik odstranite v skladu z lokalnimi/ Advarsel regionalnimi/narodnimi/mednarodnimi predpisi. Kan forårsake allergiske hudreaksjoner. Bruk vernehansker/verneklær/vernebriller/ (SK) ansiktsskjerm. VED HUDKONTAKT: Vask med Pozor store mengder vann og såpe. Ved hudirritasjon eller Môže vyvolať alergickú kožnú reakciu. -utslett: Kontakt / tilkall lege. Innholdet / emballasjen Noste ochranné rukavice/ochranný odev/ochranné skal avhendes i henhold til de lokale / regionale / okuliare/ochranu tváre. PRI KONTAKTE S nasjonale / internasjonale forskrifter. POKOŽKOU: Umyte veľkým množstvom vody a mydla. Ak sa prejaví podráždenie pokožky alebo (PL) sa vytvoria vyrážky: vyhľadajte lekársku pomoc/ Uwaga starostlivosť. Zneškodnenie obsahu/obalu v súlade s miestnymi/oblastnými/národnými/medzinárodnými Może powodować reakcję alergiczną skóry. nariadeniami. Bio-Rad 3, boulevard Raymond Poincaré 92430 Marnes-la-Coquette France Tel. : +33 (0) 1 47 95 60 00 2013/11 Fax.: +33 (0) 1 47 41 91 33 881130 www.bio-rad.com