ROLE OF OECD AND THE TEST GUIDELINES PROGRAMME IN THE REGULATORY ACCEPTANCE OF ALTERNATIVE METHODS

Transcription

1 ROLE OF OECD AND THE TEST GUIDELINES PROGRAMME IN THE REGULATORY ACCEPTANCE OF ALTERNATIVE METHODS Anne Gourmelon Principal Administrator OECD Test Guidelines Programme Environmental, Health and Safety Division

2 OECD Organisation for Economic Co-Operation and Development) Intergovernmental Organisation grouping 34 industrialised countries Austria Belgium Czech Republic Denmark Estonia Finland France Germany Greece Hungary Ireland Italy Luxembourg The Netherlands Poland Portugal Slovak Republic EU Slovenia Spain Sweden United Kingdom EUROPEAN NON-EU Iceland Israel Norway Switzerland Turkey AMERICAS Canada Chile Mexico United States ASIA - PACIFIC Australia Japan New Zealand South Korea MAD ADHERING COUNTRIES Argentina Brazil India Malaysia South Africa Singapore Thailand (prov.)

3 OECD objectives on chemical safety To help member and partner countries protect humans and the environment To gain efficiency in chemicals management by developing and harmonising testing and assessment methodologies, to avoid duplication of resources engaged by governments and industries To integrate animal welfare and 3 Rs considerations in developing these methodologies

4 Place of alternative methods at OECD? Alternatives can be test methods and non-test methods Proportion of projects dedicated to alternative test methods on the OECD Test Guidelines Programme in 2014: (27/56) compared to (6/47) seven years ago Number of projects having resulted in an alternative methods being accepted as an OECD TG: Alternatives to an existing in vivo TG procedure (12) In vitro methods that are not necessarily alternatives (7) Number of alternative test methods that failed regulatory acceptance: (2)

5 Endpoints for which alternative methods have been adopted at OECD (1) Endpoint In vivo TG Alternative TG Acute fish toxicity TG 204 TG 436 (FET) Acute oral toxicity TG 401 TG 420 (FDP, in vivo) TG 423 (ATC, in vivo) TG 425 (UDP, in vivo) Acute inhal. toxicity TG 403 TG 436 (ATC, in vivo) Skin absorption TG 427 TG 428 Phototoxicity - TG 432 (in vitro) Skin irritation/corrosion Eye irritation/corrosion TG 404 TG 405 TG 430 (corrosion, in vitro) TG 431 (corrosion, in vitro) TG 435 (corrosion, in vitro) TG 439 (irritation, in vitro) TG 437 (corrosion, ex vivo) TG 438 (corrosion, ex vivo) TG 460 (corrosion, in vitro)

6 Endpoints for which alternative methods have been adopted at OECD (2) Endpoint In vivo TG Alternative TG Skin sensitisation TG 406 (GPT) TG 429 (LLNA, in vivo) TG 442A (non radio LLNA) TG 442B (non radio LLNA) KeratinoSens (TG442D)* DPRA (TG 442C)* Under development: h-clat Genotoxicity TG 474 (micronucleus) TG 475 (chrom. abb) TG 478 (dom. lethal test) TG 483 (chrom. abb) TG484 TG 485 (transloc. assay) TG 486 (UDS) TG 488 (transgenic rodent) * Not yet formally adopted by OECD Council TG 471 (bacterial mutation) TG 473 (mamm chrom abb) TG 476 (gene mutation) TG 477 TG 479 TG 480 TG 481 TG 482 TG 487 (micronucleus)

7 What counts for the scientific acceptance? Needed but not sufficient for the regulatory acceptance Good planning of the validation study uniform test design, minimum variations chemicals selection, avoid surprises clarity in data interpretation and limitations characterise predictive capacity (sensitivity, specificity) clarity in functional limitations in the use of the assay significance of the applicability domain in light of chemical diversity

8 What helps the regulatory acceptance? A clear regulatory context in several countries clear regulatory need for an alternative assay clear intended use of the assay The scientific context resources invested in research will help emergence of various possible alternatives (from quantity will emerge quality) scientific exchange and discussions will help consensus building

9 Case of complex endpoints/ systemic toxicity Probably no more stand-alone replacement test to expect Alternative test methods building blocks to predict in vivo effects Challenge to organise the blocks to maintain efficiency of resources used, and to ensure sound and safe assessment integrated approaches to testing and assessment are essential too many alternatives is not good for regulatory acceptance if they just mirror a method preference

10 Place of testing strategies in regulatory acceptance (RA) Should testing strategies be subject to RA? Would it help RA of individual methods if testing strategies/integrated approaches were subject to RA? Can testing strategies be on equal foot as TGs at OECD? What should be developed first: TGs or ITS/IATA?

11 Important remaining issues with in vitro methods What is safe enough? issue of negatives. Differential acceptance of +/- What about toxicokinetic and metabolism? Need to understand to what a given alternative test method covers metabolism and show evidence Initially accept limitations and be clear what they are. TGs can be revised over time as experience is gained.

12 Thank you for your attention! Principal Administrator Test Guidelines Programme OECD Environment, Health and Safety Division