Product File Note Part Residues

1. Product File NotePart Residues Frédéric Joris and Bruno Dujardin Federal Public Service of Public Health, Food Chain Safety and Environment Belgium

2. Overview • When is the residue part relevant? • Contents of a Product File Note: • Key information about the a.s. • Setting of MRLs • Consumer exposure assessment • Additional studies relevant to the assessment Training Session Product File Notes and Registration Reports

3. When is the residue part relevant ? • PPP residues are likely to occur in food commodities of plant and animal origin • Example: residue data are required on feedingstuffs but not on ornementals or herbicides used on lawns, pavements, streets, railways… • From an administrative point of view, the following requests are concerned: • Application for a new registration • Application for an additional use • Application for the modification of an existing use (shorter PHI, increase in the number of application, higher dose rate) Training Session Product File Notes and Registration Reports

4. Key information about the a.s. (1) • Toxicological endpoints: consumer intake assessment • Acceptable Daily Intake (ADI): long-term risk assessment • Acute Reference Dose (ARfD): short-term risk assessment (if necessary) • Sources of toxicological endpoint • Depending on the status of the a.s. under EU review: • Review Report • EFSA scientific report • Last updated list of endpoints • DAR Training Session Product File Notes and Registration Reports

5. Key information about the a.s.(2) • Other sources of toxicological endpoints: • European MRL proposals (Working Group Pesticides Residues) • JMPR recommendations • Toxicological endpoints: values set by Scientific Institute of Public Health (Belgian Registration Committee) • Submitted residue dossier • Overview of toxicological endpoints: • Doc. 3010: combines EU and JMPR endpoints, but not updated regularly Training Session Product File Notes and Registration Reports

6. Key information about the a.s.(3) • Residue definition for products of plant and animal origin: • Parent compound only • Parent compound + significant metabolites • Metabolites only • Crop categories tested: • Five crop categories: root and tuber vegetables, leafy crops, pulses and oilseeds, fruits, cereals • Studies for crops from 3 categories indicate a similar metabolic pathway • no more studies are needed Training Session Product File Notes and Registration Reports

7. Key information about the a.s.(4) • Farm animals tested: • Ruminants: lactating cows or goats • Poultry: laying hens • If studies on ruminants and poultry are available,and metabolism is similar with rats • Extrapolation to all the animal commodities (meat, fat, edible offals, milk and eggs) • What we expect: • List of all the available metabolism studies + sources • Intended uses must be covered Training Session Product File Notes and Registration Reports

8. Key information about the a.s.: example Training Session Product File Notes and Registration Reports

9. Key information about the a.s.: example Training Session Product File Notes and Registration Reports

10. Setting of MRLs (1) • 1) a.s. with Community MRLs (harmonised a.s.) • Procedure: • An European MRL was established for the proposed use • The proposed GAP is comparable to or less critical than the GAP defended at European level • YesNo • 2) a.s. with national MRLs (unharmonised a.s.) • A complete residue data set is always needed for each applicant No further assessment is needed = the use is covered by the European evaluation A complete residue data set is needed Training Session Product File Notes and Registration Reports

11. Setting of MRLs (2) • Principles for filling in the Product File Note • Crop: a distinction must be made between field uses and protected uses ; a full data package is required for the critical situation • Proposed critical GAP: the critical practice (highest dose rate, shortest PHI, maximum number of applications) must be identified in the biology part • Residue trials: number of trials complying with the critical GAP (taking into account the 25% tolerance rule). Must be GLP and analytical methods fully validated. Training Session Product File Notes and Registration Reports

12. Setting of MRLs (3) • Principles for filling in the Product File Note • Extrapolations: trials results obtained on a crop can support the use on an another comparable crop (see guideline) • MRLs for animal products: livestock feeding studies are usually performed on ruminants (lactating cows or goats) and poultry (laying hens). Dietary burden must be stated. Training Session Product File Notes and Registration Reports

13. Setting of MRLs: example (1) Training Session Product File Notes and Registration Reports

14. Setting of MRLs: example (2) Training Session Product File Notes and Registration Reports

15. Consumer exposure assessment (1) • Models used for the chronic exposure • WHO European diet for adults (1994) • German VELS model for children aged 2-5 years (2005) • UK PSD model for ten consumer groups: adults, infants, toddlers, children (further split into 4-6 year old, 7-10 year old, 11-14 year old and 15-18 year old, vegetarians, elderly (own home), elderly (residential) (2006) • The 3 models must lead to an acceptable exposure: • < 100% ADI Training Session Product File Notes and Registration Reports

16. Consumer exposure assessment (2) • Models used for the acute exposure • German VELS model for children aged 2-5 years (2005) • UK PSD model for ten consumer groups: adults, infants, toddlers, children (further split into 4-6 year old, 7-10 year old, 11-14 year old and 15-18 year old, vegetarians, elderly (own home), elderly (residential) (2006) • For any proposed use, the 2 models must lead to • an acceptable exposure: < 100% ARfD Training Session Product File Notes and Registration Reports

17. Consumer exposure assessment (3) • Principles for filling in the Product file note: • Results from all intake models must be entered • Alternatively, intake tables from excel workbooks can be entered • Consumption data or excel workbooks can be downloaded on-line • WHO consumption data: http://www.who.int/foodsafety/chem/gems/en/index2.html • UK workbook: http://www.pesticides.gov.uk/aa_registration.asp?id=1687 • German workbook: • http://www.bfr.bund.de/cd/240 Training Session Product File Notes and Registration Reports

18. Consumer exposure assessment: example Training Session Product File Notes and Registration Reports

19. Intake table: UK chronic model Training Session Product File Notes and Registration Reports

20. Intake table: German VELS acute model Training Session Product File Notes and Registration Reports

21. Additional studies • Additional studies • Metabolism in plants and livestock: only when residue definitions are not covering the requested uses (see key information about the a.s.) • Stability of the residue during storage: when registration is sought in a certain crop group (water, oil, starch, protein or animal products), unless it has been adressed previously. • Processing studies: depending on the exposure to residues and the relevance of processed products, nature and level of residues in processed products must be adressed. • Rotational crops: when resistration is sought in a rotational crop, unless it has been adressed previously. Training Session Product File Notes and Registration Reports

22. Additional studies: example Training Session Product File Notes and Registration Reports

23. Conclusion • Every relevant section must be properly adressed (metabolism, residue trials, processing studies,…) • Always reference the submitted studies • If no study is submitted: • Clear reference to previous (EU) assessments • Or insert a scientifically valid argumentation Training Session Product File Notes and Registration Reports

24. Thank you for listening! Training Session Product File Notes and Registration Reports