Toxicidad in vitro (J. de Lapuente)

601 views
457 views

Published on

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
601
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
10
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Toxicidad in vitro (J. de Lapuente)

  1. 1. TOXICIDAD IN VITROJoaquín de LapuenteCoordinador CERETOXjlapuente@pcb.ub.cat JORNADA TOX® 1 de Febrero de 2013 Parc Científic de Barcelona
  2. 2. Uso animales EU•Sexto Informe sobre las estadísticas relativas al número de animalesutilizados para experimentación y otros fines científicos en los Estadosmiembros de la Unión Europea 120 millones de animales
  3. 3. Uso de animales en toxicologíaDECISIÓ N DE EJECUCIÓ N DE LA COMISIÓ N por la quese establece un formato común para la presentación de la informaciónprevista en la Directiva 2010/63/UE del Parlamento Europeo y delConsejo, relativa a la protección de los animales utilizados para finescientíficos [C(2012) 8064] (EEE) (2012/707/UE)
  4. 4. Necesidad racional
  5. 5. 3 Rs1960 Russel y Burch“The Principle of Humane Experimental Technique•Alternativas de Reemplazo aluden a métodos que eviten o sustituyan el uso de animales (reemplazos absolutos, reemplazos relativos).•Alternativas de Reducción aluden a cualquier estrategia que tenga como resultado el uso de un menor número de animales.•Alternativas de Refinamiento aluden a la modificación de la crí de animales o de los a procedimientos para minimizar el dolor y la angustia, asícomo para mejorar el bienestar de los animales.GreenFacts based on the Canadian Council on Animal Care, Three Rs introduction
  6. 6. Ni contigo, ni sin tí REALIDADIN VIVO A C E R CIN VITRO A M I EIN SILICO N Perdida de información T O
  7. 7. Tox in vitro Investigación (R+D)Toxicologí in vitro a Screening Regulatorio
  8. 8. InformaciónFuente WebNICEATM and ICCVAM http://iccvam.niehs.nih.gov/methods/methods.htmEURL ECVAM http://ecvam.jrc.it/Altweb 2 http://altweb.jhsph.edu/AnimAlt-ZEBET http://www.dimdi.de/static/en/db/dbinfo/zt00.htmOECD http://www.oecd.org/chemicalsafety/testing/animalwelfare.htmNIH http://nccam.nih.gov/AWI http://labanimals.awionline.org/Default.htmPrimaleLit http://primatelit.library.wisc.edu/Norina http://oslovet.norecopa.no/fag.aspx?fag=57&mnu=databases_1EURCA http://www.eurca.org/REMA http://www.remanet.net/Altbib http://toxnet.nlm.nih.gov/altbib.htmlINVITTOX http://www.invittox.com/ILAR http://dels.nas.edu/ilar/AWIC http://awic.nal.usda.gov/FishBase http://www.fishbase.org/InterNICHE http://www.interniche.org/GTEMA http://aetox.es/secciones/gtema/AltTOX http://alttox.org/ttrc/validation-ra/validated-ra-methods.htmlECOPA http://www.ecopa.eu/SOT http://www.toxicology.org/isot/ss/ivss/index.htm
  9. 9. REACH (others) APPROVAL METHODS EU Acronym Method 3 Rs Method EU Regulation method OECD Transcutaneous Electrical Resistance TER Test Replacement In vitro Directive 2000/33/EC B 40 TG 430 In Vitro Skin Corrosion: Human Skin EpiSkin™ Model Test Replacement In vitro Directive 2000/33/EC B 40 bis TG 431 In Vitro Skin Corrosion: Human Skin SKIN EpiDerm™ Model Test Replacement In vitro Directive 2000/33/EC B 40 bis TG 431 CORROSION In Vitro Skin Corrosion: Human Skin SkinEthic™ RHE Model Test Replacement In vitro Directive 2000/33/EC B 40 bis TG 431 In Vitro Skin Corrosion: Human Skin EST-1000™ Model Test Replacement In vitro Directive 2000/33/EC B 40 bis TG 431 In Vitro Membrane Barrier Test Partial CORROSITEX Method for Skin Corrosion Replacement In vitro Stage 3 TG 435 Reconstructed Human Epidermis EpiSkin™ Model Test Replacement In vitro Directive 761/2009/EC B 46 TG 439 Original Reconstructed Human Epidermis Partial Not included and not Not included and notSKIN IRRITATION EpiDerm™ Model Test Replacement In vitro foreseen B 46 foreseen Modified Reconstructed Human Epidermis EpiDerm™ SIT Model Test Replacement In vitro Directive 761/2009/EC B 46 TG 439 Reconstructed Human Epidermis SkinEthic™ RHE Model Test Replacement In vitro Directive 761/2009/EC B 46 TG 439
  10. 10. REACH (others) APPROVAL METHODS EU Acronym Method 3 Rs Method EU Regulation method OECD Partial BCOP Bovine Cornea Opacity Test Replacement In vitro L 324 2010 B 47 TG 437 Partial ICE Isolated chicken eye test Replacement In vitro L 324 2010 B 48 TG 438 Partial Not included and IRE Isolated rabbit eye tes Replacement In vitro Positive results None not foreseen yet EYE Hens egg test - chorio-allantoic Partial Not included and IRRITATION HET-CAM membrane Replacement In vitro Positive results None not foreseen yet Cytosensor Microphysiometer Partial None CM Test Replacement In vitro Not included yet Draft Partial None FL Fluorescein Leakage Test Replacement In vitro Not included yet Draft Refinement/Re LVET Low Volume Eye Test duction In vitro Not included None None Refinement/Re Directive LLNA rLLNA Local Lymph Node Assay duction in vivo 2004/73/EC B 42 TG 429 SKIN Refinement/ReSENSITISATIO LLNA DA Local Lymph Node Assay: DA duction in vivo In progress B 50 TG 422a N LLNA BrdU- Local Lymph Node Assay: BrdU- Refinement/Re Elisa Elisa duction in vivo In progress B 51 TG 422a
  11. 11. REACH APPROVAL METHODS EU Acronym Method 3 Rs Method EU Regulation method OECD RegulationMUTAGENICITY Micronucleus In vitro Micronucleus Test Reduction In vitro 1907/2006/EC TG 487 Acute oral Toxicity - Fixed Dose Reduction and FDP Procedure refinement in vivo Directive 2004/73/EC B1 bis TG 420 Acute oral toxicity - Acute Toxic ATC Class Method Reduction in vivo Directive 2004/73/EC B1 tris TG 423 Up and Down Up and Down Method Reduction in vivo Stage 3 TG 425ACUTE SYSTEM Acute Inhalation Reduction and TOXICITY Toxicity Acute Inhalation Toxicity Method refinement in vivo Stage 3 TG 436 Reduction and ATC Inhalation Acute Toxic Class Method refinement in vivo Stage 3 TG 404 Starting doses for Reduction and Guidance acute oral toxicity using in vitro test refinement Not appropriate Document 129REPEAT DOSETOXICITY Not available Embryonic Stem Cell Test for Partial until comprehensive Not included and EST Embryotoxicity Replacement In vitro valid testing strategy not foreseen yetREPRODUCTIV until comprehensive Not included and E TOXICITY MM Micromass Embryotoxicity Assay Refinement In vitro valid testing strategy not foreseen yet Whole rat Embryo Embryotoxicity until comprehensive Not included and WET Test Refinement In vitro valid testing strategy not foreseen yet 3T3NRU In vitro 3T3 NRU Phototoxicity Phototoxicity Test Replacement In vitro Directive 2000/33/EC B 41 TG 432 Regulation Skin absorption In vitro Skin Absorption Replacement In vitro 440/2008/EC B 45 TG 428 OTHER Stably Transfected Human Estrogen Receptor-alpha Transcriptional Activation Assay for Detection of Estrogenic Agonist- Reduction and STTA for EDs Activity of Chemicals refinement Stage 3 TG 436 ACUTE TOXICITY TO Guidance FISH FTA Fish Threshold Approach Reduction Strategy REACH Guidance Document 126
  12. 12. Status Validation & Regulatory Acceptance Status of Alternative Test Methods & http://alttox.org/ttrc/validation Testing Strategies -ra/validated-ra- methods.html Test Endpoint Method Name Type1 Endorsement of Scientific Validity Regulatory Acceptance International(click h ere for approved Subsequent OECD TGs, here for National/ Regional (for Endorsement(s Draft TGs, methods not yet accepted Lead Authority ) and here for GDs) internationally)Biologics & ELISA for erysipelas vaccines batchVaccines potency testing In vitro ESAC 14(2002) European Pharmacopeia ELISA for human tetanus vaccines batch potency testing In vitro ESAC 9(2000) European Pharmacopeia Draft OECD TGCarcinogenicity Cell transformation assays In vitro3 EURL ECVAM(2012) (2012) Revised US EPA Pesticide DataChronic toxicity Ending 1-year dog studies of pesticides In vivo ESAC 26(2006) RequirementsGenotoxicity Bacterial reverse mutation (Ames) test In vitro OECD TG 471 (1997) In vitro cell gene mutation test In vitro OECD TG 476 (1997) In vitrochromosomal aberration test In vitro OECD TG 473 (1997) ICCVAM comments to In vitromammalian cell micronucleus test In vitro ESAC 24(2006) OECD OECD TG 487 (2010) In vitro sister chromatid exchange test In vitro OECD TG 479 (1986) In vitrounscheduled DNA synthesis test In vitro OECD TG 482 (1986) Saccharomyces cerevisiae gene mutation assay In vitro OECD TG 480 (1986) Saacharomyces cerevisiae mitotic recombination assay In vitro OECD TG 481 (1986)Hematotoxicity:acute Colony forming unit granulocyteneutropenia macrophage (CFU-GM) assay In vitro ESAC 18(2006) Submitted to EMEA ICCVAM(2008)1 EMEA; EuropeanPyrogenicity Human whole blood IL-1 In vitro ESAC 19(2006) 3 Pharmacopeia;US agencies ICCVAM(2008)1 EMEA; European Human whole blood IL-6 In vitro ESAC 20(2006) 3 Pharmacopeia;US agencies European Pharmacopeia Limulus amebocyte lysate (LAL) test In vitro (5.0); US Pharmacopeia (85)
  13. 13. OECDOECD- Last 6 month news DeadlineDraft Test Guidelines Stage Public CommentsCytosensor Microphysiometer Test Method Early .In process February 2013Draft revised TG 437 (BCOP) and TG 438 (ICE) In process February 2013Draft revised TG 431 ( Reconstructed Human Epidermis (RhE) Test Method) In process February 2013Draft TG 473 on an in vitro Mammalian Chromosome Aberration Test In process January 2013Draft TG 487 on an in vitro Mammalian Cell Micronucleus Test PDF In process January 2013Syrian Hamster Embryo (SHE) Cell Transformation Assay In process November 2012TG 439: In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method In process November 2012TG 430: In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test Method(TER) In process November 2012TG 437: Bovine Corneal Opacity and Permeability In process October 2012TG 438: Isolated Chicken Eye Test Method In process October 2013TG 474 on an Mammalian Erythrocyte Micronucleus Test PDF In process September 2012TG 475 on an Mammalian Bone Marrow Chromosomal Aberration Test PDF In process September 2012Source: http://www.oecd.org/env/ehs/testing/section4healtheffects.htm
  14. 14. CERETOXParc Científic de Barcelona - Edifici Cluster c/Baldiri Reixac, 10-12 08028 Barcelona T. 93 403 71 83 www.pcb.ub.cat/ceretox http://goo.gl/BGLwt http://goo.gl/VBsu7

×