FRAC Mode of Action Expert Panel

1. FRAC Mode of Action Expert Panel DH / July 2012

2. Background • The annually updated list of fungicides according to mode of action (MoA) is a key document provided by FRAC (#1 accessed on www.frac.info) • In order to ensure consolidated input on classification for new inclusions to the list or on changes in mode of action classification across the companies involved in the FRAC Steering committee, it was decided in Dec 2011 to establish a MoA expert panel consisting of nominated key scientists.

3. Purpose, accountabilities, ways of working of the FRAC MoA Expert Panel The panel advices the Steering Committee on all matters relating to the mode of action of antifungal agents considered by FRAC and is responsible for the technical content of the FRAC MoA Code List and associated publications. • Scientific evaluation of information on mode of action provided by manufacturers to support classification of new inclusions to the code list or to revise current classification in case of new evidence provided • Liase with manufacturers, licensees or other responsible organizations in order to agree the mode of action of new agents as appropriate • Review new literature to pro-actively challenge current classification in the list or to propose classification of compounds listed as of unknown mode of action The panel works like an expert forum without regular face to face meetings, by sharing expert opinions on shared documents. The agreed judgements of the panel is consolidated by the chairperson of the panel and shared with the Steering commitee. The Chairperson is appointed member of the FRAC Steering committee.

4. Membershipof the FRAC MoA Expert Panel The Chair of the panel is elected by the FRAC Steering committee and is from the R&D driven agricultural industry. The chairperson is appointed member of the Steering committee. Members of the panel are nominated by the steering committee members within their R&D functions and by the chairperson of the panel. Decision on membership is by the FRAC Steering committee. Members are recognized experts in the field; they usually, but not necessarily are from the industry Current membership: • Dietrich Hermann, Syngenta – Chair • Andy Corran / Gabriel Scalliet, Syngenta – Experts • Helmut Schiffer, BASF – Expert • James Sweigard, DuPont – Expert • Klaus Tietjen, Bayer – Expert • David Young, Dow – Expert

5. Single Slide Version for presentations

6. FRAC Mode of Action Panel • Founded in 2012 to support the FRAC steering committee on matters relating the scientific evaluation of matters related to inclusion or changes of antifungal agents on the FRAC Mode of Action code list and related publications • Key objectives are: • Scientific evaluation of information on mode of action provided by manufacturers • Liase with manufacturers, licensees or other responsible organizations in order to agree the mode of action of new agents • Review new literature to pro-actively challenge current classification in the list (we are open for external inputs) • The panel operates without face to face meetings and is represented by the chairperson on the FRAC steering committee • Current membership: • Members are typically recognizedexperts in the field of mode of action • Nominated by members of the FRAC SC within their companies • Could also be non industry experts

7. FRAC Code List DH / 11.12.12

8. Open Actions on AI‘s from previous meetings Pyrimorph • should be included with the CAA molecules (H5). Action Michael Merck • Answer from China received on Dec 6th, 2012: Mr. Yang,Very pleased to receive your letter. About pyrimorph mechanism, we have done a lot of work, from the perspective of the receptor and also from the resistance mechanisms. Results from the present study showed that it either can affect the synthesis of the cell wall, but also affect the respiratory chain (complex III), so it should be a complex mechanism, but the latter is relatively weak (but stronger than fimethomorph and flumorph). Therefore, I agree to included pyrimorph in the H5 group.Best wishes!Tan Zhaohai Proposal: Include to 2013 update with CAA, H5 Dec 2012, D. Hermann FRAC SC Meeting

9. Open Actions on AI‘s from previous meetings Ametoctradin • Currently C8 QxI • French officials have listed it with QiI (C4) • Ongoing action for KK/RG to resolve with French officials • Status?

10. Open Actions on AI‘s from previous meetings Ethaboxam • Now Sumitomo (previously LG) . Classified as U5. Proposal by FRAC SC to reclassify to B3 with Zoxamide. • Valent supportive. • Sumitomo agreement received in November: B: mitosis and cell divisionTARGET SITE AND CODE: B3: ß-tubulin assembly in mitosis GROUP NAME: thiazole carboxamide CHEMICAL GROUP: ethylamino-thiazole carboxamide FRAC CODE: 22 • Proposal: reclassify from U5 to B3 in 2013 update Dec 2012, D. Hermann FRAC SC Meeting

11. Tolfenpyrad inclusion to C1 Agreed in May 12 meeting • In our May meeting we supported the request for inclusion of Tolfenpyrad from Nihon Nohyaku into C1 (complex 1 respiration) based on the following information: 1. Label inclusion several diseases in the product label in Japan: Powdery mildew : cucumber, watermelon, tomatoes, peas and eggplant Rust : Green onion White rust (Albugo) : Japanese radish, turnip and chrysanthemum 2. Recognition in practical usage – pesticide program in green onion (Japanese) listing tolfenpyrad for pest control and against rust  • Agreed by the Moa expert panel. • NN informed by me, they appreciate our decision. • Include to C1 on 2013 list FRAC SC Meeting

12. Requests for inclusion to code list by Japan FRAC Fluoromide(Nihon Noyaku) Mainly used on apple and tea as protective fungicide. Chinomethionat (AgroKanesho) Widely used to control powdery mildew on vegetables and fruit trees, etc. Ask for MoA & chemistry grouping info. Share with Expert panel for feedback Feedback received from both companies in November, circulated with expert forum, agreement to classify as multisite fungicides Proposal: Include both compounds to M in 2013 update FRAC SC Meeting

13. Fluoroimide Nihon Nohyaku provided an article on MoA from 1976 and the classification proposal FRAC SC Meeting

14. Chinomethionat Feedback AgroKanesho: An S-H inhibitor (Thiol reactive). Agreed by MoA Expert Panel FRAC SC Meeting

15. Fenpyrazamine - Sumitomo • Proposed for inclusion in 2011, but rejected by Sumitomo • Presented in Italy and Germany at conferences in 2012, remarks on similarity of MoA to Fenhexamid • Bayer (Klaus Tietjen) confirms similar MoA results for both compounds: We have now critically reviewed our results and are convinced, that Fenpyrazamine shares the mode of action with Fenhexamid: Fenpyrazamine changes the spectrum of sterols in Botrytis culture in the same way as Fenhexamid and in a way consistent with inhibition of sterol 3-ketoreductase. Fungal isolates are cross-resistant to Fenpyrazamine and Fenhexamid. • In November, Sumitomo agreed and proposes classification as follows: G: sterol biosynthesis in membranes TARGET SITE AND CODE: G3:3-keto reductase GROUP NAME: pyrazolinone (SBI: Class III) CHEMICAL GROUP: amino-pyrazolinone FRAC CODE: 17 Proposal: Include to 2013 update as proposed by Sumitomo FRAC SC Meeting

16. Tebufloquin – Meiji Seika • Proposed for inclusion 2011, but rejected by Meiji Seika • Approached again this automn, but mails no more delivered to to company restructuring • New contact established through JFRAC • Now answer received so far

17. New (pending) ISO approvals • Isofetamid, Ishihara IKF 5411: SDHI – contact details provided by JFRAC, approached ISK in early November, reply Dec 10! • Tolprocarb, Mitsui MTF 0301 Rice blast – answer: wait another year • Oxathiapiprolin, DuPont DPX-QGU42- wait for 2014 list, plan to present at Reinhardsbrunn 1 2 3 FRAC SC Meeting

18. Isofetamid Answer by ISK Dec 10: Dear Dr. Dietrich Hermann In response to your e-mail, we propose isofetamid is SDHI and should be added in category C2. We found that isofetamid exhibited no cross resistance to boscalid and other carboximide fungicides. We conducted several experiments for the possible development of resistance to isofetamid including field monitoring studies and mutation studies to generate resistant mutant in the laboratory. Based on the studies, no evidence of resistance build up risk was found. In this regard, we think it would not fit current rating “medium to high resistance risk” to isofetamid. Shigeru Mitani (Dr.) Fungicide Group Leader • Include to C2 in 2013 list? • Action for SDHI Working group to agree on wording?

19. Fenaminostrobin -> Fenaminstrobin Iso name was reviewed and now Fenaminstrobin is approved for this C3 QoI compound from Shenyang

20. Bacillus subtilis var amyloliquefaciensMBI600 inclusion • First request for inclusion via FRAG-UK in March. • Asked Andrew Brown, Becker Underwood Ltd. for more information • Detailed information was received in November • Agreement by Expert Panel this is very good quality information • Proposal: Include to F6 /44 as third product, same text as for B subtilis QST713 – for 2013 update FRAC SC Meeting

21. Bacillus subtilis var amyloliquefaciens strain Ba D747 «Double Nickel» Certis USA, licensed from Kumiai («Ecoshot») • Certis approached me during the APS meeting and provided labels and a press release in August • Some mail follow-up, but no further Mode of Action information provided • EPA approved December 2011 Proposal: include to Code 44 as other BSA strains

22. How to list biologicals • Feedback from the MoA Expert panel is that a seperate category for biologicals would be preferred , with subgroups by predominant/most likely Mode of Action. • Agreement that we need to work on a proposal, but stay with current approach for 2013 update

23. Isagro SDHI AgreWorld Daily Note - 24 September 2012 Isagro and FMC in R&D Collaboration Isagro has entered into a research and development collaboration with FMC for a new proprietary fungicide active ingredient which was discovered by the company’s IsagroRicerca subsidiary. Under the terms of the agreement, the two companies will co-develop the carboxamide fungicide product for worldwide use.