Second Announcement 7 TH INTERNATIONAL WORKSHOP ON GENOTOXICITY TESTING

Transcription

1 Secnd Annuncement 7 TH INTERNATIONAL WORKSHOP ON GENOTOXICITY TESTING At the Natinal Cancer Center Research Institute Tsukiji, Chu-ku Tky, Japan On 8 th -10 th Nvember 2017 Registratin is nw pen: 1

2 7 th Internatinal Wrkshp n Gentxicity Testing IWGT has held 6 previus wrkshps (Melburne, 1993; Washingtn, 1999; Plymuth, 2002; San Francisc, 2005; Basel, 2009, Fz d Iguacu, Brazil, 2013). The cnsensus recmmendatins frm these have been highly influential in shaping the revisins t OECD guidelines and the recmmendatins in the riginal and revised ICH S2 guidance. There are nw new challenges facing the genetic txiclgy cmmunity, new assays t cnsider, and new appraches t analysis f gentxicity data. IWGT will therefre hld its 7 th wrkshp in Tky, Japan, as a satellite meeting immediately prir t the 2017 Internatinal Cnference n Envirnmental Mutagens ICEM ( which will be held in Seul, Krea, and directly after the 46 th Meeting f the Japanese Envirnmental Mutagen Sciety JEMS ( which will be held in Tky, Japan. 2

3 At the 7 th IWGT, the fllwing Wrking Grups will be frmed: 1. A Wrking Grup n the use f 3D mdels, led by Stefan Pfuhler, USA. The fcus f the WG will be: Intrductin t the cncept f genetx testing in tissue mdels Status review f available genetx data generated in skin, liver and lung 3D tissue equivalents Validatin status f the mst develped 3D assays the 3D skin micrnucleus and cmet assays Discuss test strategy fit and develp recmmendatins 2. A Wrking Grup n emerging in vitr mammalian gentxicity systems: endpints and cell types, led by Bhaskar Gllapudi, USA. The grup will critically assess emerging in vitr tls fr measuring gene mutatins in mammalian cell cultures, cvering the fllwing pints: Basic algrithm fr strategic placement f in vitr mutatin assays Define basic principles f emerging assays Define current state f emerging assays Define research needs fr the emerging assays t make them useful fr regulatry applicatins In vitr mdels that can be used as surrgates fr predicting in viv respnse at the same lcus Higher thrughput assays that are less labrius and less expensive In vitr mdels t address mechanistic questins dealing with in viv mutagenicity Fcus grups will be: Imprving existing assays by applying new technlgies Mutatin assays using cell lines frm transgenic rdents In vitr Pig-a mutatin assays Nvel appraches t detect gene mutatins in cell cultures 3

4 3. A Wrking Grup will revisit the Salmnella mutagenicity (Ames) test, led by Rita Scheny, USA, t discuss tpics including these: Criteria fr psitive and negative respnses; e.g. is there a place fr alternatives t the 2x rule, such as Glbal Evaluatin Factrs r statistics? Criteria fr acceptable assays and cnsideratin f labratry prficiency Cnsideratin f the five mst widely used strains as well as what can be learned frm use f thers. Cnsideratin f a data-based apprach t defining a minimum strain set. Hw can strains best be maintained? Status f in silic SAR tls fr predictin f mutagenicity in the Ames test. Wuld predictins change if psitivity criteria change? 4. A Wrking Grup will discuss aspects f risk assessment f aneugens, led by Francesc Marchetti, Canada, cvering: Mlecular mechanisms f chrmsme segregatins and differences between smatic and germ cells Utility f the Adverse Outcme Pathway apprach t elucidate the mechanisms f aneuplidy Rle f aneuplidy in carcingenesis: initiatin, prmtin, r prgressin? Secndary effects f aneuplidy and their invlvement in adverse health utcmes Aneuplidy in germ cells and hereditary diseases Implicatin f aneuplidy fr human risk assessment 4

5 5. A Wrking Grup, led by David Kirkland, UK, will discuss in viv strategies: Can in vitr test utcme (mutagen, clastgen, aneugen) be used t suggest the apprpriate in viv test? Pssibility t chse a single test instead f 2 tests t fllw-up n an in vitr psitive? What can we learn frm the histrical database f verlapping TGR & cmet results? Can the cmet assay substitute fr the TGR, and in what circumstances? Are the OECD guideline default tissues (liver + site f cntact) fr the in viv cmet assay sufficient t detect expected psitives? Hw many tissues need t be tested in the cmet assay t be predictive f (a) gentxicity, (b) carcingenicity? Is there a need t include glandular stmach as well as dudenum fr site-f-cntact in the cmet assay with rally dsed substances? What is adequate expsure and the prper rute f expsure (i.p. vs ral r inhalatin) fr bne marrw MN test acceptability? Are certain tissues r rutes f expsure preferable, particularly fr the in viv MN test? Is the i.p. rute cnsidered preferable t the nrmal rute f human expsure (ral, inhalatin, dermal) because it minimizes first pass metablism in the liver? Is demnstratin f expsure in the plasma sufficient t ensure expsure f the bne marrw in a micrnucleus test? What is cnsidered insufficient bne marrw expsure that might lead t a requirement t perfrm a site-f-cntact cmet assay instead f a bne marrw MN test? Are diet and drinking water as effective as gavage dsing fr all in viv tests? What is the state f validatin f the MN assay in alternative tissues (i.e. liver, G.I. tract)? Where des the Pig-a assay fit int regulatry in viv testing? 6. Finally, a Plenary Sympsium, led by Carle Yauk, Canada, will discuss the state-f-the-science, current applicatin and added-value f high- dimensinal data in genetic txiclgy testing including: Single-mlecule sequencing Adductmics Whle genme transcriptinal prfiling High-cntent phentype-based assays 5