Section 6 Residues Anne Theobald, PRES Unit Outline Introduction - PowerPoint PPT Presentation

TG IUCLID PESTICIDE meeting 17-18 June 2020 Section 6 Residues Anne Theobald, PRES Unit

Outline Introduction Revised and new endpoint summaries Future work 2

Objective In contrast to other sections (e.g. tox, phys-chem)  “Residues” is not a standard use in IUCLID and hence not well established and tested,  only few defined, “simple” and largely GAP independent endpoints exist (e.g. residue definition, max storage time) The objective for this session is therefore to 1. check whether the six existing summary reports are fit for purpose, 2. verify that summary reports are available to capture the results from the respective endpoint study reports (OHTs) as well as for other “derived endpoints”, e.g. Maximum Residue Level (MRL), Residue Definition (RD) 3. i f missing, create new summary report templates and define which crucial endpoints (either as numeric values or information) would be useful to have in a structured manner in order to be extractable in a data base, e.g. RD, stability data 4. Identify future work needs 3

1. Check: Status Quo – six Templates CORE Template #9: Residues in food and feedingstuffs (Version [4.0]-[September 2018]) CORE Template #9.1: Metabolism in livestock (Version [2.0]-[September 2018]) CORE Template #9.2: Residues in livestock and crops (Version [2.0]-[September 2018]) CORE Template #9.3: Migration of residues into and their behaviour on food or feedingstuffs (Version [2.0]-[September 2018]) CORE Template #9.4: Expected exposure and proposed acceptable residues (Version [2.0]-[September 2018]) CORE Template #9.5: Additional information on residue chemistry (Version [2.0]-[September 2018]) The issues with current templates: With the following basic entry fields:  Titles are ambiguous (e.g. residues in livestock and crops applicable for animal AND plant?) Field name field type  Not for every chapter a separate summary template Administrative data confidentiality  Redundant? #9.3 and #9.5 Link to relevant study Link to endpoint (multiple) record(s)  Currently no entry in structured manner possible but only text Description of key information Text (rich-text area) fields Additional information Text (rich-text area)  No possibility to attach files 4

2. Verify: TOC – OHTs – Summary Report TOC Titel in IUCLID OECD OHT Endpoint Study report - Filename in DMS OECD Endpoint Summary report * - Filename in DMS 6.1 Storage stability of residues OHT_85-10_ENDPOINT_STUDY_RECORD.StabilityOfResiduesInStoredCommod.doc ENDPOINT_SUMMARY.N_StabilityOfResiduesInStoredCommod.docx Metabolism, distribution and expression of 6.2 6.2.1 OHT_85-3_ENDPOINT_STUDY_RECORD.MetabolismInCrops.doc ENDPOINT_SUMMARY.N_MetabolismInCrops.docx residues 6.2 6.2.2-4 OHT_85-2_ENDPOINT_STUDY_RECORD.MetabolismInLivestock.doc ENDPOINT_SUMMARY.MetabolismInLivestock.doc 6.2 6.2.5 fish missing ENDPOINT_SUMMARY.MetabolismInLivestock.doc 6.3 Magnitude of residue trials in plants OHT_85-5_ENDPOINT_STUDY_RECORD.ResiduesInCrops+RotationalCrops.doc ENDPOINT_SUMMARY.N_ResiduesInCrops 6.4 6.4.1-3 Feeding studies OHT_85-4_ENDPOINT_STUDY_RECORD.ResiduesInLivestock.doc ENDPOINT_SUMMARY.N_ResiduesInLivestock.docx 6.4.4 fish missing missing 6.5 6.5.1 Effect of Processing: Nature OHT_85-8_ENDPOINT_STUDY_RECORD.NatureResiduesInProcessedCommod.docx ENDPOINT_SUMMARY.N_NatureResiduesInProcessedCommod.docx Effect of Processing: Magnitude 6.5 6.5.2 OHT_85-9_ENDPOINT_STUDY_RECORD.MagnitudeResidInProcessedComm.doc ENDPOINT_SUMMARY.N MagnitudeResiduesProcessedComm.doc.docx 6.6 6.6.1 Metabolims in Rotational crops OHT 85-3 ENDPOINT SUMMARY.N RotationalCrops 6.6.2 Magnitude of residue in rotational crops OHT 85-5 6.7.1 Proposed Residue Definition n.a ENDPOINT_SUMMARY.N ResidueDefinitionPlantAnimal.doc.docx 6.7.2 Proposed MRLS ENDPOINT_SUMMARY.N MRL.doc.docx 6.8 Proposed Safety intervals n.a. n.a Estimation of the potential and actual exposure ENDPOINT_SUMMARY.ExpectedExposureAndProposedAccept 6.9 n.a. through diet and other sources ableResidues.doc Effect on the residue level in pollen and bee 6.10 6.10.1 Not_OHT_ENDPOINT_STUDY_RECORD.MagnitudeResiduesBeeProdct.doc.docx ENDPOINT SUMMARY.N_OtherStudies_.docx products Summary of information on residues in livestock 6.11 and crops Migration of residues into and their behaviour on 6.12 food or feeding stuffs Only two existing summary reports could be used and additional summary reports were needed and thus created (*files containing “N” in the file name were newly created)

Summary Reports with Tables New templates were created with basic entry fields and tables which are similar or identical to the ones currently used in the LoEP to report key findings and/or Key value for chemical safety assessment:  Storage stability (category, commodity, T, Period, Compounds, comment)  Plant metabolism (crop group, crops, application rate, application mode, DAT)  Effect of processing (standard hydrolysis study as table AND processing factors)  Rotational crops (similarity to primary crop, PECsoil, proposed restriction)

Summary Reports with Possiblity for Attachments Entry field “attached file/s of summary data” was added in summary report templates for  Metabolism (plant and animal)  Magnitude of residues in plants  Feeding studies  MRLs The aim is to allow for a transitional period attaching of files such as PRIMo, animal calculator, OECD MRL calculator, MSS composer data as XML file (until full compatibility between Metapath and IUCLID is established). Reference will be made to regulatory guidance documents were more precise information will be given.

Residue Definiton New Summary Report with basic entry fields (see slide 4) In addition: Entries creating four individual tables for  RD for plant for RA (crop group, metabolism group, treatment type, RD components, provisional)  RD for plant for monitoring (metabolism group, RD components, validated method (link), LOQ, provisional)  RD for animal for RA (animal, commodity, RD components, provisional)  RD for animal for monitoring (animal, commodity, RD components, validated method (link), LOQ, provisional) The template is intended to accommodate needs both for Peer Review (PR) and MRL applications. Subject to feasibility check, simplification could be envisaged, e.g. using guided dynamic questionnaire with conditional prompt and entries  Possibly future elaboration needed

Summarising Magniturde of Residues in Plants and MRL Proposals  Aim is to accommodate needs of MRL applications and Peer Review and to avoid double reporting of results in various summary reports as currently the case, e.g. in the LoEP for PR (MRL proposal in residue field trials and in a separate table for plant and animal commodities)  For transparency MRL proposals and results from residue field trials should be related unambiguously to RDs. Linking to the summary report for RDs might not be sufficiently clear in cases of complex RDs (different for monitoring and RA as well as different for various plant categories)  Possibility 1: Reporting in one summary report  Possibility 2: reporting in two summary reports   further discussion and decision needed

Possiblity 1: Complete Reporting in MRL summary report  Proposal for table:  Pro: all information in one table  Con: individual residue values from which a STMR, HR and MRL are derived are not transparently reported  RDs had to be entered manually either as name or as Reference # (proposal to include column for Reference # in the  summary report for RDs) In yellow: additional fields not related to MRLs but for the benefit of reporting in one place 

Possibility 2: Separate Reporting in two summary reports Proposal for table for Magnitude of residues reporting Pros:  MRL tables also includes proposals for animal Proposal for MRL table: commodities and values would need to be retrieved from the animal calculator  Individual residue levels from valid trials can be transparently reported

6.9 Estimation of the potential and actual Exposure through Diet and other Sources  Inclusion of Intake from Groundwater metabolites:  Crossreference in the template to: Groundwater metabolites and the TRV:  ENDPOINT_SUMMARY.MetabolitesGroundWater, ENDPOINT_SUMMARY.ToxicologicalReferenceValues.docx Residue definition  ENDPOINT_SUMMARY.ResidueDefinitionPlantAnimal.doc.docx  “NEW entry field: “Attached file/s of summary data”  Suggestion to attach here PRIMo as excel file.  Reference will be made to regulatory guidance documents were more precise information will be given.  Limited time for discussion whether to introduce entry fields for ADI/ARfD and results of RA (e.g. TMDI; IESTI) for dietary exposure assessment. Currently this information is contained in the to be attached PRIMo file --> Future elaboration needed

Future Work Priority 1: before release of MVP in March 2021 – agree and/or finetune 6.7.1 Residue definition 6.7.2 MRL and 6.3 Magnitude of residues Priority 2: after March 2021 6.2 Metabolism studies: Interoperabilty between IUCLID and MetaPath 6.3 Residue trials – after implementation of changes in OHT 85-5 work on IT solutions to import raw data from residue trials in IUCLID 6.7.2 MRL: implementation of OECD MRL calculator into IUCLID 6.5.2 Compatibility with Processing factor DB Priority 3: “long term vision” 6.4 Feeding study: include functionalities of animal calculator in IUCLID 6.9 Exposure: perform exposure calculation in IUCLID