Comments on the Draft Assessment Report on foramsulfuron

Transcription

1 Comments on the Draft Assessment Report on foramsulfuron Date Supplier File Belgium 01_formasulfuron_com_be.doc Denmark 02_foramsulfuron_com_dk.doc France 03_foramsulfuron_com_fr.doc France 04_foramsulfuron_com_fr-2.doc Aventis 05_foramsulfuron_com_aventis-1.doc Aventis 06_foramsulfuron_com_aventis-2.doc United Kingdom 07_foramsulfuron_com_uk.doc

2 European Commission Peer Review Programme ECCO Peer Review Meetings Full Report on Foramsulfuron Reporting table Comments on the draft assessment report Other documents considered at the meetings ECCO-Team, at: Bundesamt für Verbraucherschutz und Lebensmittelsicherheit

3 SCIENTIFIC INSTITUTE OF PUBLIC HEALTH -Louis Pasteur- Phone: Telefax: Contact person: Dr. M. DUVERGER m.duverger@iph.fgov.be Division Toxicology 01_foramsulfuron_com_be.doc your letter dated your references ECCO team BBA our references date 01/07/2001 annex(es) Concerns: new active substance under dir. 91/414/EEC Draft monograph: Foramsulfuron RMS: Germany The mammalian toxicological part of the monograph concerning foramsulfuron has been examined in details in BE. Comments on mammalian toxicology: B.6 Toxicology and metabolism B.6.1 Absorption, distribution, excretion and metabolism: Overall agreement with ADME of foramsulfuron as proposed by the RMS. Absorption: 20% Distribution: large Metabolism: limited involving 1. hydrolysis of formamide group leading to amino-aryl derivative AE F which is a minor route in rats ( %) 2. And a second pathway involves cleavage of Sulfonylurea Bridge leading to formation of AE F , which is a main pathway in rats (1.6-11%). In the metabolic pathway proposed in rats, the metabolite AE F is not included or proposed. This is not clear because as cleavage of Sulfonylurea Bridge will probably lead to AE F and to AE F as well. Moreover, in soil, AE F and AE F are the only metabolites to reach levels of > 10%. It is therefore important that mammalian metabolism covers all the identified metabolites. If this is not the case additional studies should be required. Excretion: rapid and important: essentially via faeces. B.6.2. Acute toxicity studies: No specific comments: foramsulfuron is not classified. B.6.3 Short term toxicity: 28-day rat study: Report Tox n : Purity: 90% Doses: 0, 1000, 5000 or ppm corresponding to 92, 434, and 1787 mg/bw/d. Federal Ministry of Social Affairs, Public Health And Environment Address: Juliette Wytsman 16 B-1050 BRUSSELS Phone. : Telefax:

4 2 RMS proposes as NOAEL, 5000 ppm not taking into account the decreased bw gain in females reaching 12% at this dose. We agree that no such an effect was observed in male rats but female rats might be more sensitive to the toxic effects of the compound? Moreover, it seems that a compound of lower purity was used in this study. B.6.4 Genotoxicity: Overall, the weight of evidence suggests that foramsulfuron is of no genotoxic concern. Ames test, purity 98.4%. Comment: the use of ethanol as solvent in the Ames test is not recommended. B.6.5 Long-term toxicity and carcinogenicity: Some non neoplastic and neoplastic lesions were outside the historical controls, such as: - Reduced or absent spermatozoa in epididymes at 6000 (16%) and ppm (18%). - Uterus stromal polyps at top dose of ppm(20%) - Pituitary: cysts present in males at top dose (14%) - Malignant brain astrocytoma in females (6%) The RMS does not take these effects into account. We agree that neoplastic effects observed at top dose of mg/kg bw/d are not related to the compound. NOAEL, the top dose = mg/kg bw/d (= ppm). In the endpoint listing, we consider that for the long-term toxicity, the lowest relevant NOAEL = ppm and not > ppm. Carcinogenicity study in mice: CD mice received the compound at 0, 40, 800, 8000 ppm for 80 week. NOEL = 8000 ppm = 1115 mg/kg bw/d. B Multigeneration study: Agreement with NOEL = ppm= 1234 mg/kg bw/d B Developmental toxicity studies: Agreement with RMS B ADI: Agreement with RMS B AOEL: Agreement with RMS B.6.12 Dermal absorption study in vivo: We agree with the use of 2% for dermal absorption. B.6.14: exposure data: Agreement for operator exposure and of bystander and worker Kind regards M.Duverger van Bogaert

5 ECCO PEER REVIEW PROGRAMME FULL REPORT ON FORAMSULFURON CONTENTS PART 1: REPORTS File Name 1. Conclusions (WG evaluation) Rep_0(WGeval)_Foramsulfuron Appendix 1: evaluation table rev. 1-1 (including complete list of data requirements) Appendix 2: complete list of end points 2. Report concerning all sections Rep_1(CoRAP)_Foramsulfuron PART 2: COMMENTS AND OTHER DOCUMENTS Folder name 1. Concerning all sections Documents_FR_Foramsulfuron

6 Danish Environmental Protection Agency J. no Pesticide Division 25 July 2001 CDH/STM/11 Re: ECCO Peer Review on foramsulfuron Danish comments on the monograph on foramsulfuron prepared by Germany. Overall comments The monograph seems well prepared with a detailed examination of the dossier. We have no comments to the sections concerning eco-toxicology and human toxicology. Specific comments Concerning the fate and behaviour section we have only few comments: Regarding mobility we believe it is necessary to simulate the leaching of foramsulfuron and at least the metabolites AE F15375 and AE F As the two metabolites have very low adsorption coefficients and as AE F is persistent in soil, the metabolite has a big potential for leaching to the groundwater in concentrations above 0.1 µg/l. Furthermore, the degradation of the metabolite AE F should be further addressed. Conclusion: On this background we propose a postponement of any decision on possible inclusion in Annex I until the above problems have been more investigated. W:\Wirkstoffpruefung\5. NAS\WN1\Foramsulfuron\Full Report\02_FORAMSULFURON_COM_DK.DOC 1

7 03_foramsulfuron_com_fr-1.doc MINISTERE de l'education NATIONALE et de la RECHERCHE et de la TECHNOLOGIE MINISTERE de l'agriculture et de la PÊCHE DGAL S. S. M. Structure Scientifique Mixte To: Mr Lundhen Date: Cc: ECCO TEAM (BBA) Active substance: Foramsulfuron Ecotoxicology: Comments of France on draft Monograph prepared by Germany General comments France has no additionnal requirement with regard to the European Dossier of the active substance Foramsulfuron. We agree with the proposed decision of the Rapporteur Member State, concerning the inclusion of the active substance in Annex 1. We also agree with the requirement to complete data concerning the aquatic plant Lemna gibba, because this species clearly appears to be the most sensitive to the active substance and because both classification and risk assessment are based on this data. The interpretation of the data would in general be easier with a more detailed description of the studies in Annex B, especially when they are not included in the dossier. Specific comments Document Volume 3 Point B Effects on birds, acute oral toxicity Point B.9.2. Effects on aquatic organisms Point B.9.5. Effects on non target arthropods Comment Units should be precised in studies that are performed with formulated foramsulfuron (see reference AVS ). Exposure modes are unclear for some tests, the summary indicating both static renewal system and flowthrough or static conditions (see references WAT , WAT and WAT ). The study refered as ANA : toxicity of AE F K05 A304 to the cereal aphid parasitoid Aphidius rhopalosiphi (extended laboratory test/ aged residue test ) is described three times with different results. W:\Wirkstoffpruefung\5. NAS\WN1\Foramsulfuron\Full Report\03_FORAMSULFURON_COM_FR-1.DOC

8 04_foramsulfuron_com_fr-2.doc MINISTERE de l'education NATIONALE et de la RECHERCHE et de la TECHNOLOGIE MINISTERE de l'agriculture et de la PÊCHE DGAL S. S. M. STRUCTURE SCIENTIFIQUE MIXTE To: Mr Lundhen Date: Cc: ECCO TEAM (BBA) Active substance: Foramsulfuron Identity, Physical and Chemical properties and Methods of analysis: Comments of France on draft Monograph prepared by Germany PHYSICAL AND CHEMICAL PROPERTIES No major comments on the draft monograph. Nevertheless, 2 minor comments concerning active substance : - quantum yield : did the study perform using xenon or mercury lamp? - explosive properties : did the 3 tests perform? METHODS OF ANALYSIS Analytical method for the determination of impurities in active substance : LOQ, recoveries with fortification samples and RSD% not given. It is stated that method is given in the confidential section. No validation data are given in annex C. Validation data at 0.1 µg/l are required for the confirmatory method in surface water. In air, some validation data are required for the confirmatory method VOLUME 4 ANNEX C No method and validation data seem to be given for the determination of impurities in technical active substance. In this case, results of 5 batches analysis cannot be accepted. Are the results given in table page 7, maximum values found in analysis of 5 batches or certified values. If they are maximum date, certified values are required. Results of 5 batches analysis from industrial production are required. Purity of starting material is required W:\Wirkstoffpruefung\5. NAS\WN1\Foramsulfuron\Full Report\04_FORAMSULFURON_COM_FR-2.DOC

9 05_foramsulfuron_com_aventis-1.doc Biologische Bundesanstalt für Land- und Forstwirtschaft Messeweg 11/12 D Braunschweig Attn.: Dr. Franziska Huttenlocher 30 July 2001 EU active substance testing (new active substances), our application for inclusion of the active substance foramsulfuron (AE F130360) in Annex 1 of Directive 91/414/EEC, 12291/ECCO/BBA/01, Draft Assessment Report Comments Dear Dr. Huttenlocher, Thank you very much for sending us the Draft Assessment Report dated 1 April 2001 by and in hardcopy form. In particular, many thanks for the opportunity to furnish our written comments on the Monograph. We have looked through the Monograph together with our expert departments and are now enclosing our corrections and comments in the Attachment. Yours sincerely, Aventis CropScience GmbH Dr. D. Breidert (Registration Europe) Dr. P. Haas (Registration Europe) Cc: Dr. A. Holzmann, BBA, Messeweg 11/12, D Braunschweig W. Steinheuer Attachments 1) Foramsulfuron comments on the white Monograph dated 1 April 2001, Volume 1-3 2) Aventis CropScience comments on aquatic risk assessment and calculation of TER s for Lemna gibba based on drift losses to receiving water bodies W:\Wirkstoffpruefung\5. NAS\WN1\Foramsulfuron\Full Report\05_FORAMSULFURON_COM_AVENTIS-1.DOC

10 05_foramsulfuron_com_aventis-1.doc 1) Foramsulfuron - comments on the white Monograph dated 1 April 2001, Volume 1-3 General: The numbering of the tables and figures throughout the document is not consistent. Pyrimidyl is sometimes referred to as pirimidyl. Specific comments on Volume 1: Level 1: Statement of subject matter and purpose for which the Monograph was prepared No comments Level 2: Overall conclusions Section 2.1.4, p. 12: According to viscosity Document C and its amendment C010645, risk phrase R65 (Harmful: May cause lung damage if swallowed) is not triggered for the formulation Equip. Section 2.2.3, p 13,14: The residue limit for soil is 0.05 µg/kg, the phytotoxic concentration is 0.1 µg/kg, for air 24 µg/m 3. Section , p. 14: For residues in tissues after 72 hours, the Distribution subsection gives mg equivalents/kg for renal fat of males. The concentration range is in fact mg equivalents/kg. Section , Table 2.3-1, p 16: It is stated that the technical material is not irritating to the eye. It would be more correct to say that the material was mildly irritating but no labelling is required. Section , Table 2.3-4, p 18: The dose levels for the rat combined chronic toxicity and oncogenicity study were 0, 100, 600, 6000 and ppm and not 0, 100, 600, 6000 and ppm. Section 2.4.1, p. 22: Change the following sentence: Metabolites could not be detected after application of 2-14 C-pyrimidyl foramsulfuron or U- 14 C-phenyl foramsulfuron. to Metabolites could not be detected after application at the 60 g/ha rate of 2-14 C-pyrimidyl foramsulfuron or U- 14 C-phenyl foramsulfuron. Section 2.7.3, p. 31: Metabolite AE F does carry a primary amino group, NOT a formamido group (see , Appendix II, p 49). Section 2.8.2, Appendix II, p. 50: The IUPAC chemical name for metabolite AE is: 6-formamido-1,2-benzisothiazol-3(2H)-one 1,1 dioxide The IUPAC chemical name for metabolite AE is: 6-amino-1,2-benzisothiazol-3(2H)-one 1,1 dioxide W:\Wirkstoffpruefung\5. NAS\WN1\Foramsulfuron\Full Report\05_FORAMSULFURON_COM_AVENTIS-1.DOC

11 05_foramsulfuron_com_aventis-1.doc Appendix 3: List of endpoints Section , p. 58: In the section on acute toxicity it is stated that the material is not irritating to the eye, however, the material is mildly irritating but no labelling is required. Section , p.59: In the section on long term toxicity and carcinogenicity it is noted that the target/critical effect is - slight differences from controls (increased incidences of reduced or absent spermatozoa and of pituitary cysts at the highest dose level of ppm are not considered to be adverse substance effects. Since these were not treatment-related it would be better to state that no adverse effects were seen. Section , p. 70: The correct NOEC for long-term effect of Equip on O. mykiss is 1.8 mg/l, NOT 1.1 mg/l. Section , p. 71: The correct dose level for the study on A. rhopalosiphi is 60 g as/ha, NOT 45 g as/ha. There was no effect found in this higher Tier study on mortality nor fertility, NOT 100 (Doc. C010411, and was sent to BBA on 14 November 2000). Level 4: Demand for further information (see pp. 79/80) Ecotoxicology (effects on aquatic organisms): New Lemna gibba study with the formulated product Equip will be available at 31 December Volume 3, Annex B: Section B-6.1.1, p. 79: In the final paragraph the second line should be foramsulfuron/kg and not foramsulfuron(kg. Section B , p. 111: In the third paragraph on the Materials and methods section it is stated that in addition a trial mix in week 19 was analysed. This should be week 18. W:\Wirkstoffpruefung\5. NAS\WN1\Foramsulfuron\Full Report\05_FORAMSULFURON_COM_AVENTIS-1.DOC

12 05_foramsulfuron_com_aventis-1.doc Section B , p.120: It is noted that the historical control data did not include any information on the whether the studies used to compile the data were GLP compliant and whether the studies used ethanol as a solvent for the controls and the duration of incubation for each study. This information has been requested from the laboratory performing the study. However, this information is unlikely to affect the overall conclusion of the study. Section B , p. 123: In the final paragraph of the materials and methods section the compound is wrong spelt as AE F and clearly should be AE F Section B-6.5; Table B.6.5-1, p125: The dose levels for the rat combined chronic toxicity/carcinogenicity study should be 0, 100, 600, 6000 and ppm and not 0, 100, 600, 1000 and ppm. Section B-6.5.1, p. 127: In the findings section the first two paragraphs mention dose levels of 0, 100, 600, 1000 and ppm. These need to be amended to 0, 100, 600, 6000 and ppm. Section B , p. 145: The second sentence states that the tumour incidences were slightly increased in some tissues/organs. Since there was no treatment-related effect on these parameters it would be better to state that tumour incidences were slightly higher in some tissues/organs. Section B , Table B , p.145: The dose levels for the rat combined chronic toxicity/carcinogenicity study should be 0, 100, 600, 6000 and ppm and not 0, 100, 600, 1000 and ppm. Section B , p.157: In the section on findings the grade for partial eversion should be (Grade 0 to 2) and not (Grade 0 to 1). Section B , p. 159: The conclusion would read better as follows: Equip was not a skin sensitiser in this 3-induction guinea-pig Buehler test. Because the active ingredient foramsulfuron was tested in a maximisation test and was not a sensitiser, a classification and labeling of Equip should not be required. Section B-6.12, p. 160: The first sentence of the second paragraph of the findings section should read The amount of dose associated with the application site (approximately 20% of the dose of the diluted formulation and 5 % of the neat formulation) etc. Section B-7.1.2, p. 176 Table B TRR at day 0 for the pyrimidyl label should be mg/kg not mg/kg. W:\Wirkstoffpruefung\5. NAS\WN1\Foramsulfuron\Full Report\05_FORAMSULFURON_COM_AVENTIS-1.DOC

13 05_foramsulfuron_com_aventis-1.doc Section B , p. 201 A number of figures given in the tables are not correct: Table B-8.1-3, p. 205 In the column phenyl radiolabeled compound (PH), PH 14 CO 2, day 196 should say 0.4 NOT 0.2. Table B-8.1-4, p. 205 In the column pyrimidyl radiolabeled compound (PH) PH 14 CO 2 for day 143 should say 23.0 NOT Table B-8.1-5, p. 206 In the column phenyl radiolabeled compound (PH), PH-NER for day 134 should say 56.4 NOT Figure B.8.1-1, p. 207 Metabolite AE F does carry a primary amino group, NOT a formamido group (see , Appendix II, p 49). Table B-8.1-7, p. 210 In the column phenyl radiolabeled compound (PY), the value given for AE F at day 0 should be 0.5 NOT 0.9, for day 3 should be 0.0 NOT 0.9 Table B-8.1-8, p. 210 The whole column given for others under phenyl radiolabeled components and pyrimidyl radiolabeled components needs to be corrected to the following figures: Phenyl others Pyrimdyl others Section B , p. 221 Table B , p. 226 In the column phenyl radiolabeled compound (PH), the values given for PH 14 CO 2 at day 1 should be 0.1 NOT 0.0, for day 22 should be 0.5 NOT 0.4, for day 63 should be 0.5 NOT 0.4. In the column pyrimidyl radiolabeled compound (PY), the values given for others at day 0 should be 8.3 NOT 7.0. W:\Wirkstoffpruefung\5. NAS\WN1\Foramsulfuron\Full Report\05_FORAMSULFURON_COM_AVENTIS-1.DOC

14 05_foramsulfuron_com_aventis-1.doc Table B , p. 227 In the column phenyl radiolabeled compound (PH), the values given for AE F at day 0 and 0.33 should be < LOD NOT 2.3 and 1.0. The values given for others under the same label for day 0 should be 16.4 NOT 14.1 and for day 0.33 it should be 19.3 NOT The values given for PH-NER under the same label for day 0 should be 9.1 NOT na. The values given for PH- 14 CO 2 under the same label for day 1 should be 0.1 NOT 0.0, for day 63 should be 0.6 NOT 0.4. Table B , p. 228 In the column phenyl radiolabeled compound (PH), the values given for AE F at day 1 should be < LOD NOT 0.7. Table B , p. 228 The whole column given for others under phenyl radiolabeled components and pyrimidyl radiolabeled components needs to be corrected to the following figures: Phenyl others Pyrimdyl others Table B , p. 228 In the column phenyl radiolabeled compound (PH), the values given for AE F at day 1 should be < LOD NOT The values given for others under the same label for day 0 should be 21.8 NOT Section B-8.4.2, p. 247 Table B The DT 50 value for metabolite AE at ph 4 is N/C, NOT 1.1. Section B , p Table B In the column pyrimidyl radiolabelled components, % Sum Unknowns, changes need to be made for the following days: 27/29: 1.7 NOT nd, 57: 5.0 NOT nd, 84: 6.3 NOT 1.9. For the following tables the footnotes have to be corrected: Table B (page 252) * largest single unknown 2.1% NOT 2.9 % ** largest single unknown 2.2 % SHOULD BE DELETED, is not in the table nor needed Table B (page 253) Footnotes are missing: 1 Remaining is compromised of minor components < 1% of AR and unresolved background. * largest single unknown 1.3 % ** largest single unknown 1.5 % Table B , p. 254 In the column Phenyl radiolabeled components (PH), PH 14 CO 2, on day 14 it should say 0 NOT 0.2. W:\Wirkstoffpruefung\5. NAS\WN1\Foramsulfuron\Full Report\05_FORAMSULFURON_COM_AVENTIS-1.DOC

15 06_foramsulfuron_com_aventis-2.doc Aventis CropScience 31 July ) Aventis CropScience comments on aquatic risk assessment and calculation of Toxicity/Exposure Ratios for Lemna gibba based on drift losses to receiving water bodies: The White Monograph presents Toxicity Exposure Ratios for two scenarios, a single application of 45 g a.s./ha and a single application of 60 g a.s./ha. Only TER values are given in the monograph. It is assumed that these TER s are based on drift values calculated using the default values given in the guidelines for aquatic ecotoxicology published by the commission in The assumed drift values and resultant initial (peak) PEC and TER values for Lemna (EC50 = 0.65 µg/l) are summarised in Table 1. The TER values are the same as presented in the monograph. The monograph gives TER values at 10 m of and 8.12 for the two scenarios respectively (45 g a.s./ha and 60 g a.s./ha). This assumes a drift deposition of 0.4% whereas the 95 th percentile values from the original Ganzelmeier data gives 0.3% drift at 10 meters for early applications to arable crops. Using 0.3% drift at 10 meters leads to acceptable TER values at both application rates, as shown in Table 1. Aventis believes that this is appropriate due to the fact the product will be applied at early growth stages (usually 3 to 4 leaves) Table 1 Calculation of PEC values for foramsulfuron and TER for Lemna gibba 45 g a.s./ha 60 g a.s./ha Distance Initial Initial %drift PEC TER % drift PEC TER (µg/l) (µg/l) 0 (overspray) a (10) b (0.3) (0.05) (14.44) (0.3) (0.06) (10.83) a 0.4% drift from Guidance Document on Aquatic Ecotoxicology b 0.3% drift from 95 th percentile value of original Ganzelmeier data However this assessment is relatively simple and does not take account of additional factors. 1. Deposition of drift into a water body. As outlined in our original Annex 3 tier 2 dossier and accompanying reports (Aventis Document Number B002815), the drift values given in the above table are the residues deposited at a single point, not into a water body. In order to account for the deposition across the whole width of a water body the integration of the % drift with distance curve needs to be taken into account in calculating more realistic exposure concentrations. In the original Aventis assessment two water bodies were defined representing a slow moving ditch 2 meters wide and a small farm pond 25 meters wide. As an example, Figure 1 shows the original Ganzelmeier drift deposition curve and the integrated deposition across and 2 m wide ditch and 25 m wide pond located 5 m from the edge of a treated field. W:\Wirkstoffpruefung\5. NAS\WN1\Foramsulfuron\Full Report\06_FORAMSULFURON_COM_AVENTIS-2.DOC

16 06_foramsulfuron_com_aventis-2.doc Figure 1 Deposition of Spray Drift with Distance from Edge of Treated Area. Ground Applications to Arable Crops (from Ganzelmeier et al., 1995) % of applied Distance from treated area (m) Ganzelmeier Data Interpolated 'curve' Average deposition across 2 meter ditch - 5 m buffer Average deposition across 25 meter pond - 5 m buffer From this process it is possible to calculate an average drift deposition across a water body with distance from the edge of the treated area. In this example the worst-case was the ditch and Table 2 presents the average deposition and the resultant PEC and TER values for the two scenarios (1 x 45 g a.s./ha and 1 x 60 g a.s./ha). W:\Wirkstoffpruefung\5. NAS\WN1\Foramsulfuron\Full Report\06_FORAMSULFURON_COM_AVENTIS-2.DOC

17 06_foramsulfuron_com_aventis-2.doc Table 2 Calculation of PEC values for foramsulfuron in a 2m wide ditch and TER for Lemna gibba using 95 th percentile drift values from Ganzelmeier et al., Distance from treated area (m) %drift 45 g a.s./ha 60 g a.s./ha Initial Initial PEC TER % drift PEC (µg/l) (µg/l) TER Taking into account the expected deposition across a relatively small water body 2m wide x 30 cm deep, the buffer needed to ensure a TER of > 10 is in the region of 7 to 9 m. 2. Additional drift deposition data The original Ganzelemeier et al. (1995) drift data was supplemented in 2000 and new drift deposition curves developed. These data are now used by the German BBA and according to recent presentation at the SETAC Europe conference, the data will be used within the FOCUS Surface Water Scenarios. The new deposition data for arable crops are given in Table 3. Table 3 Drift deposition data for arable crops 90 th Percentile values for updated BBA data Distance % drift 0 (overspray) Using the new drift deposition curve, it is possible to generate PEC values across a 2 m-wide ditch as given in Table 2 above. These data are presented here in Table 4 and again demonstrate that a buffer of 6 m (@ 45 g a.s./ha) and 8 m (@ 60 g a.s./ha) results in TER values of greater than 10 based on initial PEC values. W:\Wirkstoffpruefung\5. NAS\WN1\Foramsulfuron\Full Report\06_FORAMSULFURON_COM_AVENTIS-2.DOC

18 06_foramsulfuron_com_aventis-2.doc Table 4 Calculation of PEC values for foramsulfuron in a 2m wide ditch and TER for Lemna gibba using 90 th percentile drift values from updated BBA values g a.s./ha 60 g a.s./ha Distance Initial Initial %drift PEC TER % drift PEC TER (µg/l) (µg/l) Comparison of EC50 value with Time Weighted Average Concentrations The toxicity of foramsulfuron to Lemna was determined in a 7-day study. EC50 values were calculated based on the initial (0 h) concentration of the active substance in the study medium. Analysis of the test solutions at day 7 demonstrated that the initial concentrations were maintained throughout the duration of the study. However under actual use conditions foramsulfuron is degraded in surface water and so, taking into account the nature of the assessment and the extended period of the test, it is more appropriate to compare the effects on growth with an average concentration rather than an initial concentration in surface water. Respective 7-day TWA concentrations were calculated assuming initial PEC values as given in Table 2 and the rate of dissipation of foramsulfuron in the water column of sediment/water studies. These data are resummarised with corresponding TER values in Table 5. It must be noted that dilution in the slow moving water body, which will further reduce the average exposure, was not considered here. 1 Bundesanzeiger, Jahrgang 52 (2000), Nummer 100, pp W:\Wirkstoffpruefung\5. NAS\WN1\Foramsulfuron\Full Report\06_FORAMSULFURON_COM_AVENTIS-2.DOC

19 06_foramsulfuron_com_aventis-2.doc Table 5 Calculation of 7-d TWAC values for foramsulfuron in a 2m wide ditch and TER for Lemna gibba using 95 th percentile drift values from Ganzelmeier et al., Conclusion 45 g a.s./ha 60 g a.s./ha Distance 7-d 7-d %drift TWAC TER % drift TWAC TER (µg/l) (µg/l) The table of TER values presented in the White Monograph suggests a 15 m buffer is needed to achieve an acceptable margin of safety. However Aventis have given evidence that for the following reasons a buffer of only 6 m to 7 m will result in TER values of greater than 10: The standard % drift values at 10 m from the Guidelines on Aquatic Ecotoxicology used in this evaluation are different to the 95 th percentile values from the original Ganzelmeier et al tables for early applications to arable crops (0.4% vs. 0.3%) and different from the ones published in 2000 in the Bundesanzeiger as a guidance in Germany (0.29 %). Using 0.3% drift at 10 m results in acceptable TER values. Updated drift deposition data and tables from the original authors support the use of the lower value. The drift values presented in the standard tables represent deposition at a single point. When these values are considered as a deposition curve and integrated across realistic distances representing water bodies such as ditches and ponds, a buffer distance of 6 m to 8 m will result in TER values of greater than 10. The effects of foramsulfuron to Lemna were determined in studies where the concentration of the active substance was maintained throughout the duration of the 7 day test. However under actual use conditions foramsulfuron will dissipate from surface water through processes of degradation and adsorption to sediment. When the toxicity of foramsulfuron to Lemna (as given by growth of biomass) is compared to Time Weighted Average Concentrations over a 7 day period, a buffer distance of 6m to 7m will result in acceptable TER values. W:\Wirkstoffpruefung\5. NAS\WN1\Foramsulfuron\Full Report\06_FORAMSULFURON_COM_AVENTIS-2.DOC

20 07_FORAMSULFURON_COM_UK.DOC PESTICIDES SAFETY DIRECTORATE Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7PX Switchboard: GTN: Direct Dial: Fax: Int. tel: (+44) Int. Fax: (+44) mike.percival@psd.defra.gsi.gov.uk by only RMS - Jorg-Rainer Lundehn Our ref: ASY 0249 j.r.lundehn@bba.de BBA - ECCO ecco@bba.de Dear Dr Lundehn Date: 2 August 2001 RE: EC DRAFT ASSESSMENT REPORT ON FORAMSULFURON RAPPORTEUR MEMBER STATE: GERMANY EU PEER REVIEW - CORNELIA PROJECT On behalf of the Pesticides Safety Directorate of the Department for Environment, Food and Rural Affairs, UK, please find attached (at Appendix 1) our comments on the German Draft Assessment Report for the new active substance foramsulfuron. We are submitting these comments for consideration in the EU peer review procedure. I hope you find these comments useful. Yours sincerely, DR MIKE PERCIVAL PSD, UK An Executive Agency of the Department for Environment, Food and Rural Affairs W:\Wirkstoffpruefung\5. NAS\WN1\Foramsulfuron\Full Report\07_FORAMSULFURON_COM_UK.DOC

21 APPENDIX 1 PSD COMMENTS ON THE FORAMSULFURON DRAFT ASSESSMENT REPORT 1 MAMMALIAN TOXICOLOGY A well presented section, the toxicity of the active is very low indeed and PSD agrees with most of the conclusions drawn by the RMS. However, there are three areas for further consideration (PSD accepts that none of these points would prevent a recommendation for inclusion in Annex 1): Volume 1 - Section oral absorption Viewing the range of data on excretion and metabolism in volume 3, the proposed value of 20% oral absorption appears to be an over-estimate:- The urinary excretion level in the bile cannulated animals is approximately double that in other studies - a result not normally associated with bile duct cannulation. The levels of metabolites in faeces is low. The NOAEL used to set the reference values is 50 mg/kg bw/day, but the absorption value relates to 10 mg/kg bw, with evidence of reduced absorption with increased dose level. The vehicle used in the key rabbit developmental study is 1% methyl cellulose but 1% gum tragacanth was used in the ADME studies in rats. The RMS is invited to consider the comments above and review the proposal for 20% oral absorption. Volume 1 - Section toxicity of metabolites The DAR states that no plant or soil specific metabolites have been formed. Though this is strictly correct, the low level of oral absorption of the active substance and limited formation, in absolute terms of AEF in rats (<5% of administered dose) indicate this metabolite should be considered as potentially significant. AEF is present in maize at similar levels to parent (Table B7.1.2), if it is extensively absorbed orally then it could present a higher risk than the parent. PSD notes that in the case of maize the absolute residue levels are very low and for maize there are unlikely to be any concerns in terms of consumer exposures to AEF However this situation may not apply if foramsulfuron is subsequently registered for use on other crops which could result in a number of Member States (MS) considering the risks from AEF The RMS should consider preparing a more detailed assessment of the potential toxicity and relevance of AEF to a human risk assessment of foramsulfuron in general. Volume 3 - Section B Safety of non-active substances. The RMS indicates that the acute toxicity data on the formulation address the potential toxicity of the. PSD disagrees with this conclusion in respect of the safener. 2

22 Previous experience has shown that herbicide safeners exhibit significant toxicity on repeated exposures usually generating much greater concern than the active substance itself. Though safeners are not subject to 91/414/EC they are a significant issue at MS level. Foramsulfuron is unlikely to be sold without a safener and it would save duplication of effort for MS if an assessment of the toxicity and risk to operators associated with the safener were included in the DAR. 2 ENVIRONMENTAL FATE PSD are in general agreement with the DAR but have the following comments: Soil Volume 1, Level 2 (section 2.5.2) The Annex VI criteria of greater than 70% non-extractable residues and less than 5% mineralisation which was breached appears to have been addressed. However, could the RMS confirm that these aspects have been taken into account for rotational crops (see also ecotoxicology assessment below). Endpoints for soil The end points for mineralisation and % of major metabolites, particularly at 20 degrees C, needs checking. There are also no DT50 values given for any of the metabolites. A first order DT50 and bi-exponential DT90 is quoted but Volume 3 indicates the RMS is satisfied with first order kinetics for the DT50, and the DT90 could be considered as 1 st order as well. It may be helpful and less confusing if the reason for this approach was explained. PSD agrees with the DAR conclusions on adsorption/desorption/mobility. With respect to the end points, it would be helpful if the corresponding 1/n range of values for the Koc range was given. It would also be helpful if the mean Koc and 1/n values were given. The corresponding values for the major metabolites should also be entered in the end point sheet. It would be useful for the RMS to enter the full assumptions used in the PECsoil calculation in the end point sheet. Water Endpoints for water Hydrolysis - the end point sheet states there are no 'relevant' hydrolysis products. However the DAR does not specify the quantities of the metabolites which were formed, so one cannot know whether they were 'major' metabolites. 3

23 Sediment/water study end points - it would be useful to know the rate order and r2 values for the DT50 and 90 calculation if these are available. DT50 and 90 values must also be given for the major metabolites. With respect to distribution of active substance and major metabolites, the peak quantities in water and sediment for each of the compounds must be given. Water PEC - it would useful to know all the assumptions used in the water PEC calculations. Please could the RMS also explain why the PECsed has been calculated on the basis of 2cm sediment depth when the accepted method is to calculate on the basis of 5cm; the PECsed should also be calculated from the peak value and 'end of study' or 120 day value. PEC calculations should also be added for each of the major metabolites in water and sediment. It would have been helpful to have more details of the groundwater modelling conducted. One specific point concerns the mean DT50 value used. This was stated to be the mean of 5 studies. Two of the soils were studied at 25 o C, so were these values normalised to 20 o C before calculating the mean DT50? In addition, why were the major soil metabolites not modelled? As with other active substances going through the EU process, it may be helpful with respect to EU Annex I listing to conduct Tier I FOCUS groundwater modelling on this a.s. and it's major soil metabolites. ECOTOXICOLOGY PSD agrees with the conclusions drawn in the DAR on a typical sulfonylurea but have the following points to make: The Annex VI triggers of >70% NER and <5% mineralisation have been breached therefore the issue of accumulation of soil residues may need further consideration particularly in areas of continuous maize cropping. Whilst it appears that parent foramsulfuron will not accumulate, the high levels of NER present in soil after 107 days indicate that accumulation is likely to occur. Similarly in water/sediment systems high levels of NER were detected. Provided this residue is bound and not biologically available then the scientific argument of none relevance can be made. However, this issue is could be a major problem for Annex 1 listing therefore can the RMS confirm that the risk from bound residues has been adequately addressed. Overall Decision Based on toxicity of the a.s. to Lemna, the RMS proposes Annex 1 listing, with a 15 m buffer zone. A new Lemna formulation study is to be provided due to shortcomings in the MOA used in the one submitted. Endpoints from other Lemna studies, conducted using formulations containing much higher amounts of a.s. are presented, are in line with those from the Equip study. Hence the proposal to accept the biological validity of the Equip study seems reasonable. PSD agree that the main risk is to aquatic plants and that MS risk management is required. However this should be confirmed in Volume1 Level 1 Section by presenting TERs for all groups of aquatic life. [TER triggers are different for fish/invertebrates (100) and 4

24 algae/aquatic plants (10), hence it is not sufficient to provide values only for the most sensitive group.] 5

25 08_foramsulfuron_com_fr-3.doc MINISTERE de l'education NATIONALE et de la RECHERCHE et de la TECHNOLOGIE MINISTERE de l'agriculture et de la PÊCHE DGAL S. S. M. Structure Scientifique Mixte To: Mr Lundhen Date: Cc: ECCO TEAM (BBA) Active substance : Foramsulfuron Environmental Fate : Comments from France on the draft Monograph prepared by Germany General comments We generally support the evaluation of the RMS. However more information should be added in the end points and PECgw calculation (Vol. 3, B8) should be clarified. Specific comments End points Because mineralisation and non extractable RA do not meet the trigger values in the lab. studies, it would be useful to recall results from the lysimeter study to justify the lack of further demand. Rates of degradation and values of adsorption coefficients for the major metabolites have been reported in the monograph and they should be added in the end points. The lysimeter study should be reported with more details (rate of application, soil type, location, rainfall, concentration of total RA in leachate, unextractable RA in soil) Volume 3 - B.8.6 : PEC in surface water and in ground water PECgw calculation is too briefly presented. More details should be given about modelling conditions.

26 Sachb.: Ecker Datum: Austrian comments on FORAMSULFURON (RMS: DE) with regard to sections environmental fate and behaviour and ecotoxicology During our national evaluation of the foramsulfuron containing formulation FORTUNA the following comments came up: Degradation in soil (Point B.8.1 in the draft monograph) Foramsulfuron shows short DT50 values when incubated under laboratory condition. Nearly all reported studies in the draft monograph showed, that the amount of unextractable residues in soil and the mineralization rate clearly exceeds the trigger stated in Annex VI of Directive 91/414/EEC (amended by 97/57/EC): In Annex VI of the Directive (point 2.5.1, decision making) it is stated that "no authorisation shall be granted if the active substance and, where they are of significance from the toxicological, ecotoxicological or environmental point of view, metabolites and breakdown or reaction products, after use of the plant protection product under the proposed conditions of use: - during tests in the field, persist in soil for more than one year (i.e. DT90 > 1 year and DT50 > 3 months), or - during laboratory tests, form non-extractable residues in amounts exceeding 70 % of the initial dose after 100 days with a mineralization rate of less than 5 % in 100 days, unless it is scientifically demonstrated that under field conditions there is no accumulation in soil at such levels that unacceptable residues in succeeding crops occur and/or that unacceptable phytotoxic effects on succeeding crops occur and/or that there is an unacceptable impact on the environment, according to the relevant requirements provided for in points , , and " Regarding foramsulfuron no field accumulation study was performed. The amount of bound residues under field condition can be estimated from the results of a lysimeter study conducted in UK. It was shown that in one lysimeter the amount dropped down to 46 % of the applied radioactivity (AR) after approximately 4 month post application and remained by 29 % after 2 years. In the second lysimeter the concentration of bound residues remained rather

27 constant at 40 to 43 % AR from 4 month till 2 years post application. From this data it can be concluded that the level of bound residues in soil declines very slowly or could even remain stable. Two points should be considered with regard to the lysimeter study design: First, only application during one vegetation period was done (no data to estimate the concentration of bound residues in soil when applied over a period of more than one year) and, second, 14 C- pyrimidyl foramsulfuron was used. As shown in laboratory studies the concentration of bound residues was clearly higher when the phenyl-moiety of foramsulfuron was radioactive labelled. Studies on succeeding/rotational crops didn't gain further results in this special case - only single application of the active substance was used. Ecotoxicological risk assessment Yet there is a lack of data which demonstrate that no unacceptable effects will occur after using foramsulfuron on a yearly base. As foramsulfuron is used on maize it is likely that the active substance will be used in consecutive years at the same site. In our opinion the risk of bound residues has not been sufficiently addressed. According to the Guidance Document on Terrestrial Ecotoxicology, 2021/VI/98 rev. 7, page 6...the same data requirements should apply as for those substances with a DT90 (field) of > 365 days and a DT50 (field) > 3 months. Therefore we propose the following data requirements: determination of the plateau-concentration of bound residues additional tests on soil organisms as for persistent substances: laboratory test on collembola reproduction and litter-bag test. Sonja Ecker (Dept. for Pesticides)

28 Reporting table foramsulfuron (Hb) CONFIDENTIAL 12536/ECCO/BBA/01, rev. 2-1 ( ) 1/31 section 1 1. Physical/Chemical Properties; Details of Uses and Further Information; Methods of Analysis Column 1 No. Data point based on draft assessment report or comments from MS (1) Vol. 3, B Quantum yield (2) Vol. 3, B Explosive properties (3) Vol. 3 B Analytical methods Column 2 Comments from Member States or applicant F: It is not reported, whether the quantum yield study was performed using xenon or mercury lamp F: Explosive properties : did the 3 tests perform? F: Validation data at 0.1 µg/l are required for confirmatory method in surface water Column 3 Evaluation by Co-rapporteur, and (ii) Rapporteur Photodegradation study was performed using Xenon lamp (cfr. Vol. 3, B.8.4.3) (ii) Quantum yield was estimated to be zero on basis of the photolysis study, which was performed using a xenon lamp (see Vol. 3, B.8.4.3) tests (thermal sensitivity + sensitivity to shock and friction) were performed and showed no indication of explosive properties. (ii) All 3 tests were performed. None of the tests showed a danger of explosion We agree that some validation data are required for the confirmatory method in surface water; currently, only data for drinking water are available. (ii) no agreement, because the relevant limit is 0.7 µg/l Column 4 Data requirement or Open Point (if data point not addressed or fulfilled) (Annex point) Data requirement: Validation of the confirmatory method in triplicate at the relevant concentration level of 0.7 µg/l. (AIIA 4.2.3) Comments on minor typing errors are not included in the reporting table; NOT*: notifier rapporteur: DE, co-rapporteur BE

29 Reporting table foramsulfuron (Hb) CONFIDENTIAL 12536/ECCO/BBA/01, rev. 2-1 ( ) 2/31 section 1 Column 1 No. Data point based on draft assessment report or comments from MS (4) Vol. 3 B Analytical methods Column 2 Comments from Member States or applicant F: In air, some validation data required for the confirmatory method Column 3 Evaluation by Co-rapporteur, and (ii) Rapporteur We agree; the monograph reports no validation data for the confirmatory HPLCmethod (corresponding study could not be checked, since it is not in our possession) (ii) agreement, however due to particular conditions for the determination of residues in air (matrix purity) a confirmatory method should be not required, if a corresponding method was submitted for other matrices. Column 4 Data requirement or Open Point (if data point not addressed or fulfilled) (Annex point) Open point: It should be reflected that due to particular conditions for the determination of residues in air a confirmation method is possibly not required provided that corresponding methods was submitted for the other sample matrices like soil and air. Remark: Recent decisions were made in this way (e. g. last overview meeting) (AIIA4.2.4) (5) Vol. 4, C 1.1 Manufacturing process (6) Vol. 4 C Impurities F: Purity of starting material is required Although not reported in the monograph, the information is available in the dossier. Further data are thus not required (ii) agreement. Data are available in the dossier F: Are the results given in table page 7, maximum values found in analysis of 5 batches or certified values. If they are maximum date, certified values are required Max. contents in table are certified values. Further data are thus not required. (ii) unfortunately it is not clear what is meant. Comments on minor typing errors are not included in the reporting table; NOT*: notifier rapporteur: DE, co-rapporteur BE

30 Reporting table foramsulfuron (Hb) CONFIDENTIAL 12536/ECCO/BBA/01, rev. 2-1 ( ) 3/31 section 1 Column 1 No. Data point based on draft assessment report or comments from MS (7) Vol. 4, C Batch analysis Column 2 Comments from Member States or applicant F: Results of 5 batches analysis from industrial production are required. Column 3 Evaluation by Co-rapporteur, and (ii) Rapporteur This comment applies to all new a.s. Once full scale industrial production is in progress, the currently proposed technical specification will have to be compared with the analytical profile of full production batches and revised, when necessary. (ii) agreement, however this has to be handled on MS-level Column 4 Data requirement or Open Point (if data point not addressed or fulfilled) (Annex point) No need to set a data requirement and for further action, until the as will be produced in a large scale plant. If the applicant produce the as in such plant, he is obliged to submitt new batch analysis and specification to the relevant authorities Methods for determination of impurities in technical a.s. (including validation data) are reported in Annex C, p (ii) Methods and validation data are given in Annex C, pages 11 to 19. (8) Vol. 4, C Methods of analysis F: No method and validation data seem to be given for the determination of impurities in technical active substance. In this case, results of 5 batches analysis cannot be accepted. Comments on minor typing errors are not included in the reporting table; NOT*: notifier rapporteur: DE, co-rapporteur BE

31 Reporting table foramsulfuron (Hb) CONFIDENTIAL 12536/ECCO/BBA/01, rev. 2-1 ( ) 4/31 section 2 2. Environmental fate and behaviour Column 1 No. Data point based on draft assessment report or comments from MS (1) Vol.1, Fate and behaviour in soil Column 2 Comments from Member States or applicant UK:The Annex VI criteria of greater than 70% non-extractable residues and less than 5% mineralisation which was breached appears to have been addressed. However, could the RMS confirm that these aspects have been taken into account for rotational crops Column 3 Evaluation by Co-rapporteur, and (ii) Rapporteur The absence of effects on rotational crops has been verified (However, we would not agree with the paragraph B Theoretical consideration of the nature and the level of the residue). Long term effect on earthworms have been evaluated. The lysimeter study showed, that the NER accounted to 30 and 46 % of applied radioactivity after two years. These results show, that NER was reduced under natural conditions. Nevertheless, the risk assessment for nonextractable residues should be clarified by the notifier since the UP trigger is exceeded The theoretical consideration was based on soil residues available to succeeding crop plants which could be taken up via roots. In fact, in the green house experiment it has been shown that residues in rotational crops are very low after each soil ageing period (see table B.7.9-1). Column 4 Data requirement or Open Point (if data point not addressed or fulfilled) (Annex point) Data requirement: The risk assessment for nonextractable residues should be clarified by the notifier (AIIA ) Comments on minor typing errors are not included in the reporting table; NOT*: notifier rapporteur: DE, co-rapporteur BE