PLATELIA™ DENGUE IgG CAPTURE

1 plate - 96 72832Immunoassay based on immuno-capture format for qualitative detection of high level of dengue specific IgG in human serum or plasma, as an aid in diagnosis of secondary dengue infection

881100 - 2013/11

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Table of Content

1. INTENDED USE ...............................................................................3

2. SUMMARY AND EXPLANATION OF THE TEST ............................3

3. PRINCIPLES OF THE PROCEDURE ...............................................3

4. REAGENTS ......................................................................................4

5. WARNING AND PRECAUTIONS .....................................................6

6. SPECIMENS ....................................................................................8

7. PROCEDURE ...................................................................................9

8. TEST LIMITATIONS .......................................................................13

9. PERFORMANCE CHARACTERISTICS .........................................13

10. BIBLIOGRAPHY REFERENCES ....................................................15

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1- INTENTED USEPlatelia™ Dengue IgG Capture assay is a microplate immunoassay based on immuno-capture format for qualitative detection of elevated Dengue virus specific IgG in human serum or plasma. The test is intended as an aid in diagnosis of patients with clinical symptoms consistent with secondary dengue infection.

2. SUMMARY AND EXPLANATION OF THE TESTClinical course of the Dengue infection varies from asymptomatic or undifferentiated mild fever to Dengue Fever (DF), Dengue Haemorrhagic Fever (DHF) or even Dengue Shock Syndrome (DSS) potentially fatal.Differentiating between primary and secondary infection episodes is important for appropriate management of patients as it is now well documented1, 2 that secondary infection by a second serotype can lead to more severe consequences potentially fatal complications (especially DHF or DSS)3.During a secondary dengue infection, antibody titres rise rapidly and react broadly against many flaviviruses. The dominant immunoglobulin isotype is IgG which is detectable at high levels, even in the acute phase, and persists for periods lasting from 10 months to life1. Detection of specifically elevated IgG antibodies to dengue virus by immunoassay is a valuable diagnostic tool, for identification of secondary dengue infections, where the occurrence of complications in patients is higher4, 5.Platelia™ Dengue IgG Capture is an immuno-capture assay designed to detect the specific high level of Dengue IgG. This assay doesn’t detect low level of Dengue IgG Ab present from past infection. Platelia™ Dengue IgG Capture is designed to detect NS1 specific IgG useful to differentiate primary and secondary dengue virus infections 6, 7.Associating Bio-Rad Platelia™ Dengue IgG Capture assay to Bio-Rad Platelia™ Dengue NS1 Ag and Platelia™ Dengue IgA Capture assays should provide complementary information that can help, in case of elevated Dengue IgG concentration in patient sample, orientating the diagnosis towards a secondary Dengue.

3. PRINCIPLES OF THE PROCEDUREPlatelia™ Dengue IgG Capture is an immuno-capture assay performed in two steps. During the first step, the IgG antibodies present in the serum or plasma are captured by a Human anti-IgG antibody coated on the microplate. After a first washing step to remove excess of sample, conjugate formed with NS1 antigen and monoclonal anti-NS1 antibody labelled with peroxidase is added. During this second step, an immune complex anti IgG / IgG - NS1 Ag – MAb anti NS1/POD is formed and immobilized on the plate.

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After a second washing step, Chromogen reagent containing peroxidase substrate is added and incubated at room temperature which allows revealing immune complexes.The enzymatic reaction is stopped by adding 1N sulphuric acid.Optical density reading is done using a spectrophotometer at 450/620nm.

4. REAGENTSSupplied quantities of reagents have been calculated to allow 96 tests. All reagents are exclusively for in vitro diagnostic use, and must be stored at +2-8°C.

4.1. Description

Identification on label

DescriptionPresentation / preparation

72832

R1 Microplate Microplate: 12 strips of 8 breakable wells coated with human anti-IgG antibodies

1 plateReady to use

R2 Concentrated washing

solution (20X)

Concentrated washing solution (20X): Tris NaCl Buffer, pH 7.4, 2%Tween® 20Preservative: ProClin™ 300 (0.04%)

1 vial 70 ml

To be diluted

R3 Negative control

Negative control: Human serum negative for Dengue IgGTris NaCl Buffer, pH 8, 0.1% Tween® 20Preservative: Proclin™ 300 (< 0.15%)

1 vial 2.5 ml

Ready to use

R4 Calibrator Calibrator: Human serum positive for Dengue IgGTris NaCl Buffer, pH 8, 0.1% Tween® 20Preservative: Proclin™ 300 (< 0.15%)

2 vials2.5 ml

Ready to use

R5 Positive control

Positive control: Human serum positive for Dengue IgGTris NaCl Buffer, pH 8, 0.1% Tween® 20Preservative: ProClin™ 300 (< 0.15%)

1 vial2.5 ml

Ready to use

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4.2. Storage and handling requirementsThis kit should be stored at +2-8°C. Reagents can be used until the expiry date mentioned on the package (except for the specific instructions).

Identification on label

DescriptionPresentation / preparation

72832

R6 Conjugate solution (100X)

Conjugate solution (100X): Inactivated Dengue NS1 antigen coupled to monoclonal anti-NS1 IgG antibody labelled with peroxidaseBovine Serum Albumin, 0.1% Tween® 20Preservative: Proclin™ 300 (< 0.15%)

1 vial 0.30 ml

To be diluted

R7 Diluent Diluent: Tris NaCl Buffer pH 8, Tween® 20, Bovine Serum Albumin, Human serumPreservative: ProClin™ 300 (< 0.15%)

2 vials 80 ml

Ready to use

R9 Chromogen TMB

Chromogen TMB: 3.3’.5.5’ tetramethylbenzidine (TMB)

1 vial 28 ml

Ready to use

R10 Stopping solution

Stopping solution: Sulphuric acid solution (H2SO4 1N)

1 vial28 ml

Ready to use

Identification Preservation

R1 In a closed bag, 8 weeks at +2-8°C (check the presence of desiccant)

R2 Before dilution: until expiry date indicated on the label at +2-30°C in absence of contamination.After dilution: 2 weeks at +2-30°C

R3, R4, R5, R7 After opening, 8 weeks at +2-8°C in absence of contamination

R6 After opening, 8 weeks at +2-8°C in absence of contamination.After dilution, 8 hours at room temperature (+18-30°C) or up to 24h at +2-8°C

R9, R10 After opening: until expiry date indicated on the label at +2-8°C in absence of contamination

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5. WARNING AND PRECAUTIONSFor in vitro diagnostic use. For healthcare professional use.

5.1. Health and safety precautions• This test kit should be handled only by qualified personnel trained in

laboratory procedures and familiar with their potential hazards. Wear appropriate protective clothing, gloves and eye/face protection and handle appropriately with the requisite Good Laboratory Practices.

• Do not pipette by mouth.• Do not eat, drink or smoke during the handling of the samples and the

test. • The test kit contains human blood components. No known test method

can offer complete assurance that infectious agents are absent. Therefore, all human blood derivatives, reagents and human specimens should be handled as if capable of transmitting infectious disease, following recommended universal precautions for blood borne pathogens as defined by local, regional and national regulations.

• Biological spills: Human source material spills should be treated as potentially infectious.

• Spills not containing acid should be immediately decontaminated, including the spill area, materials and any contaminated surfaces or equipment, with an appropriate chemical disinfectant that is effective for the potential biohazards relative to the samples involved (commonly a 1:10 dilution of household bleach, 70-80% Ethanol or Isopropanol, an iodophor such as 0.5% Wescodyne™ Plus, etc.), and wiped dry.

• Spills containing acid should be appropriately absorbed (wiped up) or neutralized, the area flushed with water and wiped dry; materials used to absorb the spill may require biohazardous waste disposal. Then the area should be decontaminated with one of the chemical disinfectants.

NOTE: Do not place solutions containing bleach into the autoclave.

• Dispose of all specimens and material used to perform the test as though they contain an infectious agent. Laboratory, chemical or biohazardous wastes must be handled and discarded in accordance with all local, regional and national regulations.

• 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

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5.2. Precautions related to the procedure

5.2.1. Preparing• Before use wait for 30 minutes for the reagents to stabilize at room

temperature.• Do not use expired reagents.• Carefully reconstitute or dilute the reagents avoiding any contamination. • Do not mix or associate reagents from different lots within a test run.• Either Platelia™ Dengue IgG Capture and Platelia™ Dengue IgA (ref.

72831) Diluent (R7) can be used without interfering with the quality of the results.

REMARK: For Washing Solution (R2, label identification: 20X colored green), Chromogen (R9, label identification: TMB colored turquoise) and Stopping Solution (R10, label identification: 1N colored red), it is possible to use other lots than those contained in the kit, provided these reagents are strictly equivalent and the same lot is used within a given test run.

5.2.2. Processing • Do not change the assay procedure.• Do not carry out the test in the presence of reactive vapours (acid, alkaline,

aldehyde vapours) or dust that could alter the enzymatic activity of the conjugate.

• Use a new distribution tip for each sample.• Well washing is a critical step in this procedure: respect the recommended

number of washing cycles and make sure that all wells are completely filled and then completely emptied. Incorrect washings may lead to inaccurate results.

• Carefully follow the washing procedures described to obtain maximum test performance. With some instrument, it could be necessary to optimize the washing procedure (increase of number of cycle of washing step and/or volume of wash buffer for each cycle) to obtain an acceptable level of OD background for the negative sample.

• Store the reagents under recommended conditions. Do not freeze the reagents.

• Test controls and calibrator on each run.• Use glassware thoroughly washed and rinsed with deionised water or,

preferably disposable material.• Do not allow the microplate to dry between the end of the washings

operation and the reagent distribution.• Never use the same container to distribute the conjugate and the

chromogen.

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• The enzymatic reaction is very sensitive to metal or metal ions. Consequently, do not allow any metal element to come into contact with the various solutions containing the Conjugate or the chromogen TMB.

• Chromogen TMB (R9) should be colourless or light yellow. The appearance of a blue colour indicates that the reagent cannot be used and must be replaced.

• Do not expose the chromogen solution to a strong light during storage or incubation. Do not allow the chromogen solution to come in contact with any oxidizing agent.

• Do not allow the stopping solution to come in contact with any oxidizing agent, metal or metal ions.

• Do not pour in the original vial the unused conjugate.• Check the pipettes and other equipment for accuracy and correct

performance.• Make sure to cover the microplate with adhesive sealer for each

incubation at 37°C.

6. SPECIMENS Serum or plasma (EDTA, heparin or citrate) are the recommended sample types.Observe the following recommendations for handling, processing and storage of blood samples:• Collect all blood samples observing routine precaution for venipuncture.• For serum, allow samples to clot.• Keep tubes stoppered at all times.• After centrifugation, separate the serum or plasma from the clot or red

cells in a tightly stoppered storage tube.• The plasma or serum specimens can be stored at +2-8°C if test is

performed within 7 days. If test is not completed within 7 days, or for shipment, freeze the samples at -20°C or colder.

• Do not freeze/thaw samples serum samples more than 3 times. Previously frozen specimens should be thoroughly mixed (vortex) after thawing prior to testing.

• Specimens containing up to 2g/l of haemoglobin, 300mg/ml of conjugated bilirubin, 200mg/ml of non-conjugated bilirubin, 5g/l of cholesterol, 60g/l of serum-albumin, 30g/l of triolein and 120g/l of total proteins do not affect the results. However, it’s not recommended to use contaminated hyperlipemic, hyperhemolysed and hypergamma -globulinemic samples.

• Do not heat the samples.• If the specimens are to be shipped, they must be packaged in accordance

with the regulations in force regarding the transport of etiological agents and preferably transport frozen.

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7. PROCEDURE

7.1. Materials required but not provided• Distilled or deionized water• Sodium hypochlorite (bleach) and sodium bicarbonate.• Absorbent paper.• Disposable gloves.• Disposable goggles or safety glasses.• Disposable tubes.• Automatic or semi-automatic, adjustable or preset, pipettes or multi-

pipettes, to measure and dispense 10 µl to 1 000 µl, and 1 ml, 2 ml and 10 ml.

• Graduated cylinders of 1000 ml capacity.• Automatic, semi-automatic or manual microplate washer system (*).• Microplate incubator thermostatically set at 37 ± 1°C (*).• Container for biohazardous waste.• Vortex mixer.• Microplate reader equipped with 450 nm and 620 nm filters (*).(*) Consult our technical department for detailed information about the

recommended equipment.

7.2. Reagents preparation

7.2.1. Reagents to reconstitute

Reagent 2 (R2): Concentrated washing solution (20X)

Concentrated washing solution 20X to be diluted with deionised water (e.g. 50 ml of R2 + 950 ml of deionised water).

Reagent 6 (R6): Conjugate solution (100X)

Conjugate solution 100X to be diluted with R7 (e.g. 100 µl of R6 + 9.9 ml of R7).Conjugate working solution must be reconstituted at room temperature approximately one hour before use.

7.3. Assay procedureStrictly follow the assay procedure and Good Laboratory Practices.Use all controls for each run to validate the assay results and calculate the cut-off.

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1. Carefully establish the distribution and identification plan for controls and patients samples.

2. Prepare the diluted Washing Solution (R2) [Refer to Section 7.2].3. Take the carrier tray and the strips (R1) out of the protective pouch.4. All samples, controls and calibrator should be vortexed before use.Dilute all patient samples 1:101 in Diluent (R7) (e.g. by adding 5 µl of sample

to 500 µl of Diluent (R7)). Do not dilute Controls and Calibrator.Thoroughly mix diluted samples.5. Distribute in the well in the following order (advisable plate distribution):• 200 µl of negative control (R3) in well A1,• 200 µl of calibrator (R4) in wells B1, C1,• 200 µl of positive control (R5) in well D1,• 200 µl of the first sample in well E1,• 200 µl of the second sample in F1, etc.6. Reconstitute the Conjugate working solution (R6) [Refer to Section 7.2]7. Cover the microplate with a microplate cover or wrap film. Immediately incubate the microplate in a thermostat controlled water bath

or in a dry incubator for 1 hour ± 5 minutes at 37°C ± 2°C.8. At the end of the incubation period, remove the microplate cover or wrap

film. Aspirate the content of all wells into a container for biohazard waste (containing sodium hypochlorite). Invert the microplate and gently tap on adsorbent paper to remove remaining liquid. Wash microplate 4 times with 350 µl of diluted Washing Solution (R2) with careful removal of the remaining liquid by microplate inversion and tapping on absorbent paper after each wash.

9. Immediately distribute 200 µl of Conjugate working solution (R6) into all wells. The solution must be gently shaken before use.

10. Cover the microplate with a microplate cover or wrap film. Immediately incubate the microplate in a thermostat controlled water bath

or in a dry incubator for 1 hour ± 5 minutes at 37°C ± 2°C.11. At the end of the incubation period, remove the microplate cover or wrap

film. Aspirate the content of all wells into a container for biohazard waste (containing sodium hypochlorite). Invert the microplate and gently tap on adsorbent paper to remove remaining liquid. Wash microplate 4 times with 350 µl of diluted Washing Solution (R2) with careful removal of the remaining liquid by microplate inversion and tapping on absorbent paper after each wash.

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12. Immediately and away from light distribute 200 µl of Chromogen TMB (R9) into each well. Allow the reaction to develop in the dark for 30 ± 5 minutes at room temperature (+18-30°C). Do not use adhesive plate sealer during this incubation.

13. Stop the enzymatic reaction by adding 100 µl of Stopping Solution (R10) in each well. Use the same sequence and pace of distribution as for the development solution.

14. 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.

15. Before reporting results, check for agreement between the reading and the distribution plan of plate and samples.

7.4. Quality ControlInclude the calibrator and controls for each microplate and for each run, and analyse the obtained results. [Refer to Section 7.5]

7.5. Calculation / Interpretation of the results

7.5.1. Calculation of the Cut-Off value (CO)The Cut-Off value (CO) corresponds to the mean value of the optical densities (OD) of the Calibrator duplicates (R4).

7.5.2. Calculation of the sample ratioSample Ratio = OD sample / CO

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7.6. Interpretation of the results

7.7. Test validation criteriaFor validation of the assay, the following criteria must be met:

If validation criteria above are not met, the test run should be repeated.

Sample ratio Result Interpretation

Ratio < 0.90 Negative Non detectable high level of Dengue IgG antibody.A negative result is presumptive of absence of secondary dengue infection.Complementary testing with acute Dengue infection diagnostic assays (e.g. Bio-Rad Platelia™ Dengue NS1 Ag and/or Platelia™ Dengue IgA Captures assays) should be performed to rule out acute Dengue infection.

0.90 ≤ Ratio < 1.10 Equivocal No elevated level of Dengue IgG can be determined. Sample should be retested with an alternative method to confirm or rule out a secondary dengue infection or the test should be repeated on another sample collected a few days later.

Ratio ≥ 1.10 Positive Presence of detectable high level of Dengue IgG antibody. A positive result is presumptive of secondary dengue infection: recently exposed or currently infected patients.Diagnostic should also include clinical symptoms and biological data.

Validation criteria

R3 Ratio R3 = OD (R3) / CO ≤ 0.15

R4OD mean ≥ 0.200.90 x CO value < R4i < 1.10 x CO value

R5 Ratio R5 = OD (R5) / CO ≥ 1.30

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8. TEST LIMITATIONS• Samples obtained very early in the infection may not have high detectable

IgG antibodies. It’s recommended to test suspected acute infections with Platelia™ Dengue NS1 Ag and/or Platelia™ Dengue IgA Capture to rule out acute Dengue infection.

• Convalescent samples taken from primary dengue infected individuals may have high detectable level of Dengue IgG Ab. It is recommended to test samples within 6-15 days for accurate primary and secondary differentiation.

• Definitive diagnosis of Dengue Secondary infection should not only be made on Platelia™ Dengue IgG Capture results. It should also include clinical symptoms and other biological data.

• Serological cross-reactivity with other flaviviruses (e.g.Yellow fever, West Nile, Japanese encephalitis viruses) is common. Infections with these viruses must be excluded before confirmation of dengue diagnosis.

• Specimens with high concentrations of gamma globulins may produce false negative results.

9. PERFORMANCE CHARACTERISTICS

9.1. Precision measurementFour samples were analysed 24 times in the same run for the repeatability testing and twice a day during 20 days for the reproducibility study. For each sample, the mean, the standard deviation and the coefficient of variation (CV) were calculated using the corresponding ratios.

9.1.1 Repeatability

9.1.2. Intermediate reproducibility

ratio SD CV (%)

S1 0.14 0.015 4.30

S2 0.31 0.006 4.90

S3 0.73 0.022 3.00

S4 1.19 0.043 3.60

ratio SD CV (%)

S1 0.155 0.030 19.6

S2 0.300 0.031 10.2

S3 0.718 0.045 7.5

S4 1.185 0.111 9.4

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9.2. Clinical performance

9.2.1. Diagnostic specificityThe specificity of the PLATELIA™ DENGUE IgG Capture has been determined by testing 201 samples: 49 sera from French blood donors, 50 sera from healthy Indian donors, 51 sera from healthy Honduran donors and 51 sera from dengue-like syndrome febrile patients for which Dengue diagnostic was excluded. Two equivocal were found with Healthy Honduras donors. Specificity is 99% (199/201) with a confidence interval of 95% of 96.47-99.85%.

9.2.2. Comparison of results for PLATELIA™ DENGUE IgG Capture versus a commercial Dengue IgG Capture assay for the detection of secondary infection

An internal study on 82 sera from Asian patients with clinically confirmed Dengue was conducted and compared to a commercial Dengue IgG Capture assay for the detection of secondary infection.

Equivocal samples were excluded from calculation since retesting was not conducted. The positive percent agreement is 91.89% (34/37) with a 95% exact confidence interval of 78.09%-98.30% and the negative percent agreement is 90.48%(38/42) with a 95% exact confidence interval of 77.38-97.34%.

An external study on well documented 130 samples from French Guiana patients with clinically confirmed Dengue was conducted and compared to a commercial Dengue IgG Capture assay for the detection of secondary infection.

Platelia™ Dengue IgG Capture

Dengue Status Negative Equivocal Positive Total

Primary 38 2 4 44

Secondary 3 1 34 38

Total 41 3 38 82

Platelia™ Dengue IgG Capture

Dengue Status Negative Equivocal Positive Total

Primary 17 3 5 25

Secondary 0 3 102 105

Total 17 6 107 130

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Equivocal samples were excluded from calculation since retesting was not conducted. The positive percent agreement is 100% (102/102) with a 95% exact confidence interval of 96.45%- 100% and the negative percent agreement is 77.3%(17/22) with a 95% exact confidence interval of 54.63%-92.18%.

Including the combined internal study and the French Guiana study, the overall agreement with the reference assay is 94.08% (191/ 203) with a 95% exact confidence interval of 89.90% -96.91%. The percent of equivocal samples not included in the calculation was 4.24%.

9.3. Analytical Specificity / Cross reactivity studyA panel of 50 specimens from patients with other infections than Dengue was tested with PLATELIA™ DENGUE IgG Capture. 1 equivocal was found with patients infected by West Nile Virus and was not included. 30 sera containing heterophile antibodies HAMA (n=10), anti-nuclear antibodies ANA (n=10) or Rheumatoid Factor (n=10) were tested with Platelia™ Dengue IgG Capture assay.No positive reactions were noted. The analytical specificity is 100% (79/79).

10. BIBLIOGRAPHY REFERENCES1. World Health Organization and the Special Programme for Research and

Training in Tropical Diseases (TDR) ; Dengue guidelines for diagnosis, treatment, prevention and control: new edition ; 2009

2. Centers for Disease Control and Prevention ; Dengue Laboratory Guidance and Diagnostic Testing ;

http://www.cdc.gov/dengue/clinicallab/laboratory.html 3. Dengue viremia titer, antibody response pattern, and virus serotype

correlate with disease severity. Vaughn DW et al, J Infect Dis. 2000 Jan;181(1):2-9.

4. Kinetics of non-structural protein 1, IgM and IgG antibodies in dengue type 1 primary infection. Hu D et al. Virol J. 2011 Feb 2;8:47. doi: 10.1186/1743-422X-8-47.

5. Laboratory diagnosis of primary and secondary dengue infection. Schilling S et al. J Clin Virol. 2004 Nov;31(3):179-84.

6. Comparison of capture immunoglobulin M (IgM) and IgG enzyme-linked immunosorbent assay (ELISA) and nonstructural protein NS1 serotype-specific IgG ELISA for differentiation of primary and secondary dengue virus infections. Shu PY et al.Clin Diagn Lab Immunol. 2003 Jul;10(4):622-30.

7. Human Dengue antibodies against structural and nonstructural proteins. Valdés K et al. Clin Diagn Lab Immunol. 2000 Sep;7(5):856-7.

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(CZ)Nebezpečí Způsobuje těžké poleptání kůže a poškození očí. Může vyvolat alergickou kožní reakci. Používejte ochranné rukavice/ochranný oděv/ochranné brýle/obličejový štít. PŘI ZASAŽENÍ OČÍ: Několik minut opatrně vyplachujte vodou. Vyjměte kontaktní čočky, jsou-li nasazeny a pokud je lze vyjmout snadno. Pokračujte ve vyplachování. PŘI POŽITÍ: Vypláchněte ústa. NEVYVOLÁVEJTE zvracení. PŘI STYKU S KŮŽÍ (nebo s vlasy): Veškeré kontaminované části oděvu okamžitě svlékněte. Opláchněte kůži vodou/osprchujte. Při podráždění kůže nebo vyrážce: Vyhledejte lékařskou pomoc/ošetření. Obsah/nádobu likvidujte v souladu s místními/regionálními/národními/mezinárodními předpisy.

(DE)Gefahr Verursacht schwere Verätzungen der Haut und schwere Augenschäden. Kann allergische Hautreaktionen verursachen. Schutzhandschuhe/Schutzkleidung/Augenschutz/Gesichtsschutz tragen. BEI KONTAKT MIT DEN AUGEN: Einige Minuten lang behutsam mit Wasser spülen. Vorhandene Kontaktlinsen nach Möglichkeit entfernen. Weiter spülen. BEI VERSCHLUCKEN: Mund ausspülen. KEIN Erbrechen herbeiführen. BEI KONTAKT MIT DER HAUT (oder dem Haar): Alle beschmutzten, getränkten Kleidungsstücke sofort

ausziehen. Haut mit Wasser abwaschen/duschen. Bei Hautreizung oder -ausschlag: Ärztlichen Rat einholen/ärztliche Hilfe hinzuziehen. Entsorgung des Inhalts / des Behälters gemäß den örtlichen / regionalen / nationalen/ internationalen Vorschriften.

(DK)FareForårsager svære forbrændinger af huden og øjenskader. Kan forårsage allergisk hudreaktion. Bær beskyttelseshandsker/beskyttelsestøj/øjenbeskyttelse/ansigtsbeskyttelse VED KONTAKT MED ØJNENE: Skyl forsigtigt med vand i flere minutter. Fjern eventuelle kontaktlinser, hvis dette kan gøres let. Fortsæt skylning. I TILFÆLDE AF INDTAGELSE: Skyl munden. Fremkald IKKE opkastning. VED KONTAKT MED HUDEN (eller håret): Tilsmudset tøj tages straks af/fjernes. Skyl/brus huden med vand. Ved hudirritation eller udslet: Søg lægehjælp. Bortskaffelse af indholdet/beholderen i henhold til de lokale/regionale/nationale/internationale forskrifter.

(EE)Ettevaatust Põhjustab rasket nahasöövitust ja silmakahjustusi. Võib põhjustada allergilist nahareaktsiooni. Kanda kaitsekindaid/kaitserõivastust/kaitseprille/kaitsemaski. SILMA SATTUMISE KORRAL: loputada mitme minuti jooksul ettevaatlikult veega. Eemaldada kontaktläätsed, kui neid kasutatakse ja kui neid on kerge eemaldada. Loputada veel kord. ALLANEELAMISE KORRAL: loputada suud. MITTE kutsuda esile oksendamist. NAHALE (või juustele) SATTUMISE KORRAL: võtta viivitamata kõik saastunud rõivad seljast. Loputada nahka veega/loputada duši all. Nahaärrituse või _obe korral: pöörduda arsti poole. Sisu/konteineri käitlus vastavuses kohalike/regionaalsete/rahvuslike/rahvusvaheliste nõuetega.

(EN)DangerCauses severe skin burns and eye damage. May cause an allergic skin reaction. Wear protective gloves/protective clothing/eye protection/face protection. IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. IF SWALLOWED: rinse mouth. Do NOT induce vomiting. IF ON SKIN (or hair): Remove/Take off immediately all contaminated clothing. Rinse skin with water/shower. If skin irritation or rash occurs: Get medical advice/attention. Dispose of contents/container in accordance with local/regional/national/international regulations.

(ES)Peligro Provoca quemaduras graves en la piel y lesiones oculares graves. Puede provocar una reacción alérgica en la piel. Llevar guantes que aíslen del frío/gafas/máscara.

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EN CASO DE CONTACTO CON LOS OJOS: Aclarar cuidadosamente con agua durante varios minutos. Quitar las lentes de contacto, si lleva y resulta fácil. Seguir aclarando. EN CASO DE INGESTIÓN: Enjuagarse la boca. NO provocar el vómito. EN CASO DE CONTACTO CON LA PIEL (o el pelo): Quitarse inmediatamente las prendas contaminadas. Aclararse la piel con agua o ducharse. En caso de irritación o erupción cutánea: Consultar a un médico. Eliminar el contenido o el recipiente conforme a la reglamentación local/regional/nacional/internacional.

(FI)Vaara Voimakkaasti ihoa syövyttävää ja silmiä vaurioittavaa. Voi aiheuttaa allergisen ihoreaktion. Käytä suojakäsineitä/suojavaatetusta/silmiensuojainta/kasvonsuojainta. JOS KEMIKAALIA JOUTUU SILMIIN: Huuhdo huolellisesti vedellä usean minuutin ajan. Poista piilolinssit, _edical voi tehdä helposti. Jatka huuhtomista. JOS KEMIKAALIA ON NIELTY: Huuhdo suu. EI saa oksennuttaa. JOS KEMIKAALIA JOUTUU IHOLLE (tai hiuksiin): Riisu saastunut vaatetus välittömästi. Huuhdo/suihkuta iho vedellä. Jos ilmenee ihoärsytystä tai ihottumaa: Hakeudu lääkäriin. Säilytä säiliö(t) noudattaen paikallisia/alueellisia/kansallisia/kansainvälisiä määräyksiä.

(FR)DangerProvoque des brûlures de la peau et des lésions oculaires graves. Peut provoquer une allergie cutanée. Porter des gants de protection/des vêtements de protection/un équipement de protection des yeux/du visage. EN CAS DE CONTACT AVEC LES YEUX: rincer avec précaution à l’eau pendant plusieurs minutes. Enlever les lentilles de contact si la victime en porte et si elles peuvent être facilement enlevées. Continuer à rincer. EN CAS D’INGESTION: rincer la bouche. NE PAS faire vomir. EN CAS DE CONTACT AVEC LA PEAU (ou les cheveux): enlever immédiatement les vêtements contaminés. Rincer la peau à l’eau/se doucher. En cas d’irritation ou d’éruption cutanée: consulter un médecin. Éliminer le contenu/récipient conformément à la réglementation locale/régionale/nationale/internationale.

(GR)Κίνδυνος Προκαλεί σοβαρά δερματικά εγκαύματα και οφθαλμικές βλάβες. Μπορεί να προκαλέσει αλλεργική δερματική αντίδραση. Να φοράτε προστατευτικά γάντια/προστατευτικά ενδύματα/μέσα ατομικής προστασίας για ταμάτια/πρόσωπο. ΣΕ ΠΕΡΙΠΤΩΣΗ ΕΠΑΦΗΣ ΜΕ ΤΑ ΜΑΤΙΑ: Ξεπλύνετε προσεκτικά με νερό για αρκετά λεπτά. Εάν υπάρχουν φακοί επαφής, αφαιρέστε τους, εφόσον είναι εύκολο. Συνεχίστε να ξεπλένετε. ΣΕ ΠΕΡΙΠΤΩΣΗ ΚΑΤΑΠΟΣΗΣ: Ξεπλύνετε το στόμα. ΜΗΝ προκαλέσετε εμετό. ΣΕ ΠΕΡΙΠΤΩΣΗ ΕΠΑΦΗΣ ΜΕ ΤΟ ΔΕΡΜΑ (ή με τα μαλλιά): Αφαιρέστε αμέσως

όλα τα μολυσμένα ενδύματα. Ξεπλύνετε το δέρμα με νερό/στο ντους. Εάν παρατηρηθεί ερεθισμός του δέρματος ή εμφανιστεί εξάνθημα: Συμβουλευθείτε/Επισκεφθείτεγιατρό. Απορρίψτε τα περιεχόμενα/δοχείο σύμφωνα με τους τοπικούς/εθνικούς/διεθνείς κανονισμούς.

(HR)OpasnostUzrokuje teške opekline kože i ozljede oka. Može izazvati alergijsku reakciju na koži. Nositi zaštitne rukavice/zaštitnu odijelo/zaštitu za oči/zaštitu za lice. U SLUČAJU DODIRA S OČIMA: oprezno ispirati vodom nekoliko minuta. Ukloniti kontaktne leće ukoliko ih nosite i ako se one lako uklanjaju. Nastaviti ispiranje. AKO SE PROGUTA: isprati usta. NE izazivati povraćanje. U SLUČAJU DODIRA S KOŽOM (ili kosom): odmah ukloniti/skinuti svu zaganenu odjeću. Isprati kožu vodom/tuširanjem. U slučaju nadražaja ili osipa na koži: zatražiti savjet/pomoć liječnika. Odložite sadržaje /spremnike u skladu s lokalnim/regionalnim/nacionalni/međunarodnim odredbama.

(HU)Veszély Smarkiai nudegina odą ir pažeidžia akis. Allergiás bőrreakciót válthat ki. Védőkesztyű/védőruha/szemvédő/arcvédő használata kötelező. SZEMBE KERÜLÉS esetén: Több percig tartó óvatos öblítés vízzel. Adott esetben a kontaktlencsék eltávolítása, ha könnyen megoldható. Az öblítés folytatása. LENYELÉS ESETÉN: a szájat ki kell öblíteni. TILOS hánytatni. HA BŐRRE (vagy hajra) KERÜL: Az összes szennyezett ruhadarabot azonnal el kell távolítani/le kell vetni. A bőrt le kell öblíteni vízzel/zuhanyozás. Bőrirritáció vagy kiütések megjelenése esetén: orvosi ellátást kell kérni. Az edény tartalmát / a tartályt a helyi/regionális/nemzeti/nemzetközi szabályozásoknak megfelelően kell hulladékként elhelyezni.

(IT)PericoloProvoca gravi ustioni cutanee e gravi lesioni oculari. Può provocare una reazione allergica cutanea. Indossare guanti/indumenti protettivi/Proteggere gli occhi/il viso. IN CASO DI CONTATTO CON GLI OCCHI: sciacquare accuratamente per parecchi minuti. Togliere le eventuali lenti a contatto se è agevole farlo. Continuare a sciacquare. IN CASO DI INGESTIONE: sciacquare la bocca. NON provocare il vomito. IN CASO DI CONTATTO CON LA PELLE (o con i capelli): togliersi di dosso immediatamente tutti gli indumenti contaminati. Sciacquare la pelle/fare una doccia. In caso di irritazione o eruzione della pelle: consultare un medico. Smaltire il prodotto/recipiente in conformità con le disposizioni locali / regionali / nazionali / internazionali.

(LT)PavojingaSmarkiai nudegina odą ir pažeidžia akis. Gali sukelti

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alerginę odos reakciją. Mūvėti apsaugines pirštines/dėvėti apsauginius drabužius/naudoti akių (veido) apsaugos priemones. PATEKUS Į AKIS: Kelias minutes atsargiai plauti vandeniu. Išimti kontaktinius lęšius, jeigu jie yra ir jeigu lengvai galima tai padaryti. Toliau plauti akis. PRARIJUS: išskalauti burną. NESKATINTI vėmimo. PATEKUS ANT ODOS (arba plaukų): Nedelsiant nuvilkti/pašalinti visus užterštus drabužius. Odą nuplauti vandeniu/čiurkšle. Jeigu sudirginama oda arba ją išberia: kreiptis į gydytoją. Turinį/talpą išpilti (išmesti) - šalinti pagal vietines / regionines / nacionalines / tarptautines taisykles.

(NL)Gevaar Veroorzaakt ernstige brandwonden en oogletsel. Kan een allergische huidreactie veroorzaken. Beschermende handschoenen/beschermende kleding/oogbescherming/gelaatsbescherming dragen. BIJ CONTACT MET DE OGEN: voorzichtig afspoelen met water gedurende een aantal minuten; contactlenzen verwijderen, indien mogelijk; blijven spoelen. NA INSLIKKEN: de mond spoelen — GEEN braken opwekken. BIJ CONTACT MET DE HUID (of het haar): verontreinigde kleding onmiddellijk uittrekken — huid met water afspoelen/afdouchen. Bij huidirritatie of uitslag: een arts raadplegen. De inhoud en de verpakking verwerken volgens de plaatselijke/regionale/nationale/internationale voorschriften.

(NO)FareForårsaker alvorlige hudforbrenninger og øyeskader. Kan forårsake allergiske hudreaksjoner. Bruk vernehansker/verneklær/vernebriller/ansiktsskjerm. VED KONTAKT MED ØYNENE: Skyll forsiktig med vann i opptil flere minutter. Fjern evt. kontaktlinser såfremt dette er lett mulig. Fortsett skyllingen. VED SVELGING: Skyll munnen. IKKE fremkall brekninger. VED HUDKONTAKT (eller kontakt med hår): Alle tilsølte klær må fjernes straks. Vask/dusj huden med vann. Ved hudirritasjon eller -utslett: Kontakt / tilkall lege. Innholdet / emballasjen skal avhendes i henhold til de lokale / regionale / nasjonale / internasjonale forskrifter.

(PL)NiebezpieczeństwoPowoduje poważne oparzenia skóry oraz uszkodzenia oczu . Może powodować reakcję alergiczną skóry. Stosować rękawice ochronne/odzież ochronną/ochronę oczu/ochronę twarzy. W PRZYPADKU DOSTANIA SIĘ DO OCZU: Ostrożnie płukać wodą przez kilka minut. Wyjąć soczewki kontaktowe, jeżeli są i można je łatwo usunąć. Nadal płukać. W PRZYPADKU POŁKNIĘCIA: wypłukać usta. NIE wywoływać wymiotów. W PRZYPADKU KONTATKU ZE SKÓRĄ (lub z włosami): Natychmiast usunąć/zdjąć całą zanieczyszczoną odzież. Spłukać skórę pod strumieniem wody/prysznicem. W przypadku wystąpienia podrażnienia skóry lub wysypki: Zasięgnąć porady/zgłosić się pod opiekę lekarza. Zawartość / pojemnik usuwać zgodnie z przepisami miejscowymi / regionalnymi / narodowymi /

międzynarodowymi.

(PT)PerigoProvoca queimaduras na pele e lesões oculares graves. Pode provocar uma reacção alérgica cutânea. Usar luvas de protecção/vestuário de protecção/protecção ocular/protecção facial. SE ENTRAR EM CONTACTO COM OS OLHOS: enxaguar cuidadosamente com água durante vários minutos. Se usar lentes de contacto, retire-as, se tal lhe for possível. Continuar a enxaguar. EM CASO DE INGESTÃO: enxaguar a boca. NÃO provocar o vómito. SE ENTRAR EM CONTACTO COM A PELE (ou o cabelo): despir/retirar imediatamente toda a roupa contaminada. Enxaguar a pele com água/tomar um duche. Em caso de irritação ou erupção cutânea: consulte um médico. Eliminar o conteúdo/recipiente de acordo com a legislação local/regional/nacional/internacional.

(RO)Pericol Provoacă arsuri grave ale pielii şi lezarea ochilor. Poate provoca o reacţie alergică a pielii. Purtaţi mănuşi de protecţie/îmbrăcăminte de protecţie/echipament de protecţie a ochilor/ chipament de protecţie a feţei. ÎN CAZ DE CONTACT CU OCHII: clătiţi cu atenţie cu apă timp de mai multe minute. Scoateţi lentilele de contact, dacă este cazul şi dacă acest lucru se poate face cu uşurinţă. Continuaţi să clătiţi. ÎN CAZ DE ÎNGHIŢIRE: clătiţi gura. NU provocaţi voma. ÎN CAZ DE CONTACT CU PIELEA (sau părul): scoateţi imediat toată îmbrăcămintea contaminată. Clătiţi pielea cu apă/faceţi duş. În caz de iritare a pielii sau de erupţie cutanată: consultaţi medicul. Aruncaţi conţinutul/containerul în acord cu regulamentele locale/regionale/naţionale/internaţionale.

(SE)Fara Orsakar allvarliga frätskador på hud och ögon. Kan orsaka allergisk hudreaktion. Använd skyddshandskar/ skyddskläder/ ögonskydd/ ansiktsskydd. VID KONTAKT MED ÖGONEN: Skölj försiktigt med vatten i flera minuter. Ta ur eventuella kontaktlinser om det går lätt. Fortsätt att skölja. VID FÖRTÄRING: Skölj munnen. Framkalla INTE kräkning. VID HUDKONTAKT (även håret): Ta omedelbart av alla nedstänkta kläder. Skölj huden med vatten/duscha. Vid hudirritation eller utslag: Sök läkarhjälp. Innehållet / behållaren avfallshanteras enligt lokala / regionala / nationella / internationella föreskrifter.

(Sl)NevarnoPovzroča hude opekline kože in poškodbe oči. Lahko povzroči alergijski odziv kože. Nositi zaščitne rokavice/zaščitno obleko/zaščito za oči/zaščito za obraz. PRI STIKU Z OČMI: previdno izpirajte z vodo nekaj minut. Odstranite kontaktne leče, če jih imate in če to lahko storite brez težav. Nadaljujte z izpiranjem. PRI ZAUŽITJU: izprati usta.

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 881100 www.bio-rad.com

NE izzvati bruhanja. PRI STIKU S KOŽO (ali lasmi): takoj odstraniti/sleči vsa kontaminirana oblačila. Izprati kožo z vodo/prho. Če nastopi draženje kože ali se pojavi izpuščaj: poiščite zdravniško pomoč/oskrbo. Vsebino/vsebnik odstranite v skladu z lokalnimi/regionalnimi/narodnimi/mednarodnimi predpisi.

(SK)NebezpečenstvoProvoacă arsuri grave ale pielii şi lezarea ochilor. Môže vyvolať alergickú kožnú reakciu. Noste ochranné rukavice/ochranný odev/ochranné okuliare/ochranu tváre. PO ZASIAHNUTÍ OČÍ:

Niekoľko minút ich opatrne vyplachujte vodou. Ak používate kontaktné šošovky a ak je to možné, odstráňte ich. Pokračujte vo vyplachovaní. PO POŽITÍ: vypláchnite ústa. Nevyvolávajte zvracanie. PRI KONTAKTE S POKOŽKOU (alebo vlasmi): Odstráňte/vyzlečte všetky kontaminované časti odevu. Pokožku ihneď opláchnite vodou/sprchou. Ak sa prejaví podráždenie pokožky alebo sa vytvoria vyrážky: vyhľadajte lekársku pomoc/starostlivosť. Zneškodnenie obsahu/obalu v súlade s miestnymi/oblastnými/národnými/medzinárodnými nariadeniami.