PEER REVIEW REPORT ON METRAFENONE 16.01.2006 TABLE OF … · PEER REVIEW REPORT ON METRAFENONE...

PEER REVIEW REPORT ON METRAFENONE 16.01.2006

TABLE OF CONTENTS Document File Name 00 Cover page 00 metrafenone cover.doc 01 All comments received on the DAR 01 metrafenone all comments.doc 02 Reporting table all sections 02 metrafenone rep table rev1-1.doc 03 All reports from EPCO Expert Meetings 03 metrafenone all reports.doc 04 Evaluation table 04 metrafenone eval table rev1-2.doc List of all reports from EPCO Expert Meetings Date Name Section 31.01.-03.02.2005 EPCO Expert Meeting 16 Environmental Fate and Behaviour 31.01.-04.02.2005 EPCO Expert Meeting 17 Ecotoxicology 21.-25.02.2005 EPCO Expert Meeting 18 Mammalian Toxicology 23.-25.02.2005 EPCO Expert Meeting 19 Residues 01.-03.03.2005 EPCO Expert Meeting 20 Physical and Chemical Properties

EPCO Expert Meeting 16 (31 January – 03 February 2005) 17253/EPCO/BVL/05 Metrafenone 02 February 2005

REPORT OF EPCO EXPERT MEETING 16 METRAFENONE Rapporteur Member State: United Kingdom Specific comments on the active substance in the section 4. Environmental Fate and Behaviour are already listed in the relevant reporting table. Comments submitted for this meeting are listed below. 1. Comments submitted for this meeting:

None

2. Documents submitted for meeting:

Date Supplier File Name November 2004 RMS/United Kingdom Metrafenone addendum 1

(Nov2004).doc 09.06.2004 RMS/United Kingdom Metrafenone consultation report

(09-06-2004).doc 25.11.2004 RMS/United Kingdom Metrafenone evaluation table rev0-1

(25-11-2004).doc 25.11.2004 RMS/United Kingdom Metrafenone list of end points (25-

11-2004).doc December 2004 RMS/United Kingdom Metrafenone list of essential studies

(Dec2004).doc 14.07.2004 RMS/United Kingdom Metrafenone reporting table rev1-1

(14-07-2004).doc 20.01.2005 RMS/United Kingdom Metrafenone Metabolites 2005-01-

20.doc 3. Documents tabled at the meeting:

None The conclusions of the meeting were as follows: 4. Data on preparations: BAS 560 00 F and BAS 560 02 F 5. Classification and labelling: R53 6. Recommended restrictions/conditions for use: none 7. Reference List: see general report 8. Table of metabolites: will be clarified bilaterally between EFSA and RMS

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EPCO Expert Meeting 16 (31 January – 03 February 2005) 17253/EPCO/BVL/05 Metrafenone 02 February 2005

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Areas of concern: Persistence in soil

Appendix 1: EPCO discussion table: METRAFENONE

Appendix 2: Evaluation table

EPCO Expert Meeting 16 (31 January – 03 February 2005) 17253/EPCO/BVL05 Metrafenone 02 February 2005 Appendix 1: Discussion Table, Metrafenone (Fu) 4. Environmental Fate and Behaviour No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert

Meeting

Open point 4.1: RMS to provide an addendum with final results of field accumulation studies and experts meeting to discuss it in the context of the persistence issue. Refer to reporting table 4(2), See also comments 4(5), 4(6), 4(7), 4(9) and 4(10).

An addendum is available with the assessment of the updated results of the accumulation field study after five years of repeated application. RMS informed the meeting that actual risk assessment presented in the DAR was done on results of accumulation modelling with worst case input parameters and PEARL leaching model. In the RMS’s opinion, the results of the field study confirmed the values predicted by modelling. Study does not provide any indications for suspecting that the accumulation rate will be higher than showed in modelling. RMS introduced the question how many years an accumulation study should last in general and if the notifier should prolong this specific study. Some experts raised the concern that data from the german field shows that plateau level is not reached after 5 years. They were of the opinion that, in order to come to a final conclusion, the plateau should be reached and therefore the study continued. Experts discussed whether further data were necessary, taking into account that assumptions in the model were worst case: worst case DT50 from laboratory studies on aerobic degradation in soil and worst case Koc were employed in the modelling exercise. The appropriateness of using the PEARL leaching model for calculating PECsoil, as done in this case, was also discussed. The applicability of the model for calculation of plateau-PECsoil was implicitly accepted by the experts in this case. Nevertheless, a number of experts still have the strong feeling that the field study should be continued, in order to confirm the results with respect to reaching the plateau level in soil after repeated annual applications of metrafenone.

Open point closed. Applicability of model for calculation of plateau-PECsoil has been implicitly accepted by the experts in this case. Nevertheless, a number of experts still have the strong feeling that the field study should be continued, in order to confirm the results with respect to reaching the plateau level in soil after repeated annual applications of metrafenone.

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EPCO Expert Meeting 16 (31 January – 03 February 2005) 17253/EPCO/BVL05 Metrafenone 02 February 2005 No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert

Meeting

Open point 4.2: Assessment of surface water contamination through drain flow and runoff to be discussed in an experts meeting. RMS will try to provide FOCUS sw in an addendum.

RMS informed the meeting that the standard approach for assessing surface water contamination at the time of dossier submission and DAR preparation was based on spray drift, whereas FOCUS surface water was not required at that time. A respective assessment had been provided in the original DAR (p. 381). Drain flow PECsw additionally presented in the DAR were based on the UK approach used for national authorisations, while runoff was not assessed. In the opinion of the RMS, the risk assessment provided should be sufficient for reaching a conclusion at EU level. EFSA co-chair stated that when the product is applied by spray, it is usually assumed that spray drift is the main route for contamination of surface water bodies. However, a particular problem for this specific substance lies in its high persistence in soil. Therefore, concerns on potential contamination through drain flow and runoff may arise as well. It was discussed by the experts whether spray drift is seen to contribute primarily to the load surface water or whether also runoff and drain flow can be regarded as major routes for contamination of surface water in this case. Most of experts were of the opinion that runoff and drainage are of limited significance, due to the properties of the active substance (high Koc). Runoff would be off minor importance than erosion, but also the latter less important than spray drift. To address drain flow, the UK national approach can be used here as indicative. Guidance on the drain flow calculation provided in the original DAR are available on the PSD homepage: click on: ‘Applicant Advice’ > ‘Data Requirement Handbook’ > ‘Chapter 6: Environmental Fate and Behaviour’ > ‘Open PDF’ > ‘Section 5: Method for calculation of Predicted Environmental Concentration in Surface Water (PECsw) for Exposure via Drainflow’ The calculation provided by the RMS confirmed the assumption that drain flow was of minor importance, since levels in surface water by drainage are covered by the values calculated for spray drift. The meeting therefore agreed that in this case loadings to surface water from drainflow and runoff are expected to be lower than loadings due to spray drift and do not need to be considered for finalising the EU risk assessment. MS may need to pay special attention to runoff and drainflow in their national authorisation procedures.

Open point closed. The meeting agreed that in this case loadings to surface water from drain flow and runoff are expected to be lower than loadings due to spray drift and do not need to be considered for finalising the EU risk assessment. MS may need to pay special attention to runoff and drain flow in their national authorisation procedures.

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EPCO Expert Meeting 16 (31 January – 03 February 2005) 17253/EPCO/BVL05 Metrafenone 02 February 2005 No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert

Meeting

4.1 Notifier to submit final report of field accumulation studies. (Scheduled for August)

Latest results and final report are still not available. However, updated interim results were submitted by the notifier. These results were considered by the RMS in an addendum and discussed in the meeting under open point 4.1.

Data requirement still open. Latest results and final report are still not available. However, updated interim results were submitted by the notifier. These results were considered by the RMS in an addendum and discussed in the meeting under open point 4.1.

New open point 4.3: RMS to revise the list of end points according the amendments proposed by EPCO 16.

The list of end points was revised in the meeting and the following amendments were proposed: Soil: state that after 5 years plateau has not been reached, synopsis with modelling results suggested. Soil adsorption: amend Kf-values with appropriate units Air, volatilisation: include vapour pressure Photochemical oxidative degradation: include version of Atkinson programme and concentration of hydroxyl radicals Sediment: add for clarification that a bulk density of 1.3 g/cm3 has been used Definition of residues: Include occurring metabolites, no explanatory statement needed for the list of end points. Include photolysis metabolite (indicate photolysis origin in brackets).

Open point still open.

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Evaluation table, Metrafenone (Fu) EU RESTRICTED 16822/EPCO/BVL/04 rev. 1-0 (02.02.05) section 4 – Environmental fate and behaviour

Appendix 2: Evaluation table 4. Environmental Fate and Behaviour No.

Column A Conclusions of the EFSA Evaluation Meeting

Column B Comments from the main data submitter / applicant on the EFSA Evaluation Meeting conclusion

Column C Rapporteur Member State comments on main data submitter / applicant comments

Column DRecommendations EPCO Expert Meeting / Conclusions of the evaluation group

Section 4Data requirements: 1 Open points: 2


Open point 4.1. RMS to provide an addendum with final results of field accumulation studies and experts meeting to discuss it in the context of the persistence issue. Refer to reporting table 4(2), See also comments 4(5), 4(6), 4(7), 4(9) and 4(10).

Evaluation of five year results is detailed in addendum. Results of these studies indicate that the original conclusions regarding accumulation of metrafenone presented in the DAR are still valid, as are the risk assessments based on the subsequent exposure assessment. The applicant is proposing that sufficient information has been provided to support Annex I listing and they have provided a reasoned case to support finalisation of the field accumulation studies at this time. See Addendum.

EPCO 16 (31.01 – 03.02 2005):Open point closed. Applicability of model for calculation of plateau-PECsoil has been implicitly accepted by the experts in this case. Nevertheless, a number of experts still have the strong feeling that the field study should be continued, in order to confirm the results with respect to reaching the plateau level in soil after repeated annual applications of metrafenone.

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No.





Open point 4.2 Assessment of surface water contamination through drain flow and runoff to be discussed in an experts meeting. RMS will try to provide FOCUS sw in an addendum. Refer to reporting table 4(13)

At the time the notifier submitted the dossier and when the UK was finalising the technical input to the DAR it was not possible to use the FOCUS surface water modelling tools as they were not available. These tools did not become available until May/June 2003. Where the spray drift will contribute to surface water exposure it is appropriate for input by drainage and runoff and any risk mitigation required to protect aquatic life from these routes of entry to be considered at the member state level. There will be situations where drainage and runoff will not occur. Therefore there are safe uses and an Annex 1 listing decision can and should be made without the need for a FOCUSsw assessment. At the time of writing of the DAR drainflow was incorporated into the document for UK national consideration only.

EPCO 16 (31.01 – 03.02 2005):Open point closed. The meeting agreed that in this case loadings to surface water from drain flow and runoff are expected to be lower than loadings due to spray drift and do not need to be considered for finalising the EU risk assessment. MS may need to pay special attention to runoff and drain flow in their national authorisation procedures.

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No.





4.1 Notifier to submit final report of field accumulation studies. (Scheduled for August)

Notifier has submitted a second interim report on field accumulation studies (5th year) on 4 August 2004. The studies have been extended for an additional year (2004-2005). A request to finalize the field accumulation studies was submitted to PSD on 29 October 2004. See addendum.

See open point 4.1. EPCO 16 (31.01 – 03.02 2005):Data requirement still open. Latest results and final report are still not available. However, updated interim results were submitted by the notifier. These results were considered by the RMS in an addendum and discussed in the meeting under open point 4.1.


EPCO 16 (31.01 – 03.02 2005):Open point still open.

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Evaluation table, Metrafenone (Fu) EU RESTRICTED 16822/EPCO/BVL/04 rev. 1-0 (02.02.05) List of representative uses evaluated List of representative uses evaluated*

Crop and / or situation

(a)

Member State

or Country

Product name

F G or I

(b)

Pests or Group of

pests controlled

(c)

Formulation

Application

Application rate per treatment

PHI (days)

(l)

Remarks:

(m) Type Conc.

(d-f)

of as

(i)

method kind

(f-h)

growth stage & season

(j)

number min max

(k)

interval between

applications (min)

kg as/hl

min max

water l/ha

min max

kg as/ha

min max

Cereals

Northern & Southern Europe

BAS

560 00 F

F

Powdery mildew Erysiphe graminis

SC

300 g/L

over plant spray

30 – 79

1 – 2

21

0.150

100-400

0.15–0.038

35

Cereals


BAS

560 00 F

F

Eyespot Pseudocercosporella herpotrichioides

SC

300 g/L

over plant spray

30 – 35

1

-

0.150

100-400

0.15-0.038

-

Grapevines

Northern Europe

BAS

560 02 F

F

Powdery mildew Uncinula necator

SC

500 g/L

over plant spray

15 – 81

1 – 8

12

0.1

1000

0.010

28

Grapevines

Southern Europe

BAS

560 02 F

F


SC

500 g/L

over plant spray

57 – 81

1 – 8

12

0.1

1000

0.010

28

Water volume applied in function of the crop size and application technique

Remarks: * Uses for which risk assessment could not been concluded due to lack of essential (h) Kind, e.g. overall, broadcast, aerial spraying, row, individual plant, between data are marked grey the plants - type of equipment used must be indicated (a) For crops, the EU and Codex classifications (both) should be used; where relevant, (i) g/kg or g/l the use situation should be described (e.g. fumigation of a structure) (j) Growth stage at last treatment (BBCH Monograph, Growth Stages of Plants, (b) Outdoor or field use (F), glasshouse application (G) or indoor application (I) 1997, Blackwell, ISBN 3-8263-3152-4), including where relevant, information on (c) e.g. biting and suckling insects, soil born insects, foliar fungi, weeds season at time of application (d) e.g. wettable powder (WP), emulsifiable concentrate (EC), granule (GR) (k) The minimum and maximum number of application possible under practical (e) GCPF Codes - GIFAP Technical Monograph No 2, 1989 conditions of use must be provided (f) Method, e.g. high volume spraying, low volume spraying, spreading, dusting, drench (l) PHI - minimum pre-harvest interval (g) All abbreviations used must be explained (m) Remarks may include: Extent of use/economic importance/restrictions

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EPCO Expert Meeting 17 (31 January – 04 February 2005) 17250/EPCO/BVL/05 Metrafenone 31 January 2005

REPORT OF EPCO EXPERT MEETING 17 METRAFENONE Rapporteur Member State: UNITED KINGDOM Specific comments on the active substance in the section 5. Ecotoxicology are already listed in the relevant reporting table. Comments submitted for this meeting are listed below. 1. Comments submitted for this meeting:

Date Supplier File Name


Date Supplier File Name November 2004 RMS/United Kingdom Metrafenone addendum 1

(Nov2004).doc 09.06.2004 RMS/United Kingdom Metrafenone consultation report

(09-06-2004).doc 25.11.2004 RMS/United Kingdom Metrafenone evaluation table rev0-1

(25-11-2004).doc 25.11.2004 RMS/United Kingdom Metrafenone list of end points (25-

11-2004).doc December 2004 RMS/United Kingdom Metrafenone list of essential studies

(Dec2004).doc 14.07.2004 RMS/United Kingdom Metrafenone reporting table rev1-1

(14-07-2004).doc 3. Documents tabled at the meeting:


The conclusions of the meeting were as follows: 4. Data on preparations: BAS 560 00 F for cereals and BAS 560 02 F for grape vine. 5. Classification and labelling: N, R50/53. 6. Recommended restrictions/conditions for use: none. 7. Reference List

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EPCO Expert Meeting 17 (31 January – 04 February 2005) 17250/EPCO/BVL/05 Metrafenone 31 January 2005

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Areas of concern: Appendix 1: EPCO discussion table: METRAFENONE


EPCO Expert Meeting 17 (31 January – 04 February 2005) 17250/EPCO/BVL/05 Metrafenone 31 January 2005 Appendix 1: Discussion Table, Metrafenone (Fu) 5. Ecotoxicology No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert

Meeting

Open point 5.1: RMS to include results of the studies on soil respiration and nitrification with soil metabolite CL377160 and formulation BAS 560 02 F in the list of endpoints. Refer to reporting table 5(2)

RMS stated that the endpoints were amended. Meeting accepted this.

EPCO 17 (31.01. – 04.02.2005)Open point fulfilled.

Open point 5.2: RMS to provide risk assessment for earthworm consuming birds in an addendum. Refer to reporting table 5(7)

RMS explained that there is a brief summary in the evaluation table why RMS beliefs that the risk to earthworms is acceptable. MS asked to put this statement in an addendum. RMS will prepare a new addendum only when it is necessary and asked if this could be sufficient. EFSA stated that regarding the Kow of 1995 a 2 at the end was forgotten (= 19952). A worst-case soil PEC of 0.843 mg a.s./kg soil is for cereals while the real worst case is for vines. The PEC for vines is higher. This has to be amended. The calculation of the ETE for birds (0.93 mg/kg bw)is not reproducible. The accumulation plateau for the PEC plus additional applications should be used regarding the use of vine because there are several applications foreseen. The PECtwa

EPCO 17 (31.01. – 04.02.2005)Open point still open. RMS to prepare an addendum to correct the BCF for earthworms and the ETE for earthworm eating birds and mammals and amend the risk to earthworm eating birds and mammals accordingly

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EPCO Expert Meeting 17 (31 January – 04 February 2005) 17250/EPCO/BVL/05 Metrafenone 31 January 2005 No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert

Meeting

including the accumulation plateau should thus be used (General report). The RMS clarified that the approach that would be taken would be to cover the maximum accumulated total PECsoil (as for the original assessment). Obviously this value is higher than the PECtwa.

Open point 5.3: EFSA proposes the RMS to provide a risk assessment for fish eating birds and mammals according to SANCO/4145/2000 in an addendum. Refer to reporting table 5(9)

RMS hasn’t done this. The guidance document on terrestrial ecotoxicology SANCO/10329/2002 rev2 finalised 17 October 2002 states in the introduction that ‘For new active substances the document should be implemented for dossiers submitted from 1 August 2003.’ Although such a clear statement is not made in the Birds and Mammals document SANCO/4145/2000, dated 25 September 2002 it is considered that the same principle applies which is a more theoretical risk than a practical risk. The Meeting changed the open point: RMS to verify PECsw values used in the original DAR for the risk assessment of fish eating birds and mammals as a different PECsw-value for birds and mammals was used.

EPCO 17 (31.01. – 04.02.2005)Open point still open. RMS to verify PECsw values used in the original DAR for the risk assessment of fish eating birds and mammals,.

Open point 5.4.: RMS to calculate risk for earthworm consuming mammals in an addendum. Refer to reporting table 5(12)

See open point 5.2 EPCO 17 (31.01. – 04.02.2005)See open point 5.2

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EPCO Expert Meeting 17 (31 January – 04 February 2005) 17250/EPCO/BVL/05 Metrafenone 31 January 2005 No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert

Meeting

Open point 5.5: RMS to evaluate new litter bag study and include study summary and risk assessment in an addendum. Refer to reporting table 5(18) See also comments 5(19) and 5(20).

The summary of this study is available on page 40 of the addendum. This addresses the risk to soil processes. MS asked if the 60 % degradation control has been reached in this study. RMS noted that this is not presented in the summary of the study in the DAR. The RMS contacted a colleague and was able to confirm during the meeting that 61.7 % degradation was found in the control. The meeting agreed that this point is addressed.


Open point 5.6: Pending on the outcome of the discussion of open point 4.2 with regard to the assessment of surface water contamination through drain flow and runoff, a revised risk assessment for aquatic organisms may be necessary. Refer to reporting table 5(11)

RMS stated that until we have FOCUSsw the contamination through drainflow and runoff can not be calculated. Meeting agreed to wait for the outcome of the fate discussion. It was concluded that this further work was not necessary for the Annex I listing but of course MS’s can do their own risk assessment if they wish. Referred to the discussion table of the section on fate and behaviour (EPCO 16)

EPCO 17 (31.01. – 04.02.2005)See discussion table of fate and behaviour section (EPCO 16)

Residue definition Soil compartment CL 377160; risk was less than for the active substance. Thus the metabolite was not regarded as relevant. Surface water, sediment and ground water: only a.s. was regarded as relevant.

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Evaluation table, Metrafenone (Fu) EU RESTRICTED 16822/EPCO/BVL/04 rev. 1-0 (31.01.05) section 5 – Ecotoxicology


5. Ecotoxicology No.





Section 5Data requirements: - Open points: 6

Section 5Data requirements: 0 Open points: 2 Data gaps:0

Open point 5.1: RMS to include results of the studies on soil respiration and nitrification with soil metabolite CL377160 and formulation BAS 560 02 F in the list of endpoints. Refer to reporting table 5(2)

List of endpoints has been amended. However it is considered that the aim of the endpoint sheets is to display the definitive worst case endpoints for use in risk assessments. The end points list had complied with this and listed the relevant information.


Open point 5.2: RMS to provide risk assessment for earthworm consuming birds in an addendum. Refer to reporting table 5(7)

Although a detailed risk assessment has not been carried out, the residue in earthworms has been assessed and is 0.28 mg/kg worm calculated according to SANCO4145/2000, assuming a Kow of 1995, a Koc of 3105 and a worst case soil PEC of 0.843 mg/kg soil. The ETE for birds is calculated by multiplying the residue in worms by 1.1. This is 0.93 mg/kg/bw. As this is below

EPCO 17 (31.01. – 04.02.2005)Open point still open. RMS to prepare an addendum to correct the BCF for earthworms and the ETE for earthworm eating birds and mammals and amend the risk to earthworm eating birds and mammals accordingly

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No.





the exposure predicted to occur via other routes for which the risk has been assessed to be acceptable, there are no concerns about the risk from exposure via earthworms.

Open point 5.3: EFSA proposes the RMS to provide a risk assessment for fish eating birds and mammals according to SANCO/4145/2000 in an addendum. Refer to reporting table 5(9)

At the time of submission of this application the guidance document had not been agreed and as such was not included in the evaluation The guidance document on terrestrial ecotoxicology SANCO/10329/2002 rev2 finalised 17 October 2002 states in the introduction that ‘For new active substances the document should be implemented for dossiers submitted from 1 August 2003.’ Although such a clear statement is not made in the Birds and Mammals document SANCO/4145/2000, dated 25 September 2002 it is considered that the same principle applies. As this dossier was submitted for evaluation in June 2002 the RMS has not revised the risk assessment. It is proposed that adequate methods of assessment have been used and as indicated in the reporting table 5(9) the risk to fish eating birds and mammals is considered acceptable.

EPCO 17 (31.01. – 04.02.2005)Open point still open. RMS to verify PECsw values used in the original DAR for the risk assessment of fish eating birds and mammals,.

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No.





Open point 5.4.: RMS to calculate risk for earthworm consuming mammals in an addendum. Refer to reporting table 5(12)

Although a detailed risk assessment has not been carried out, the residue in earthworms has been assessed and is 0.28 mg/kg worm calculated according to SANCO4145/2000, assuming a Kow of 1995, a Koc of 3105 and a worst case soil PEC of 0.843 mg/kg soil. The ETE for mammals is calculated by multiplying the residue in worms by 1.4. This is 1.18 mg/kg/bw. As this is below the exposure predicted to occur via other routes for which the risk has been assessed to be acceptable, there are no concerns about the risk from exposure via earthworms.

EPCO 17 (31.01. – 04.02.2005)open point closed. See open point 5.2

Open point 5.5: RMS to evaluate new litter bag study and include study summary and risk assessment in an addendum. Refer to reporting table 5(18) See also comments 5(19) and 5(20).

Evaluation of revised litter bag study is detailed in addendum. Results indicate that the risks to soil degradation processes are acceptable.


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No.





Open point 5.6: Pending on the outcome of the discussion of open point 4.2 with regard to the assessment of surface water contamination through drain flow and runoff, a revised risk assessment for aquatic organisms may be necessary. Refer to reporting table 5(11)

See open point 4.2. EPCO 17 (31.01. – 04.02.2005)See discussion table of fate and behaviour section (EPCO 16)

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Evaluation table, Metrafenone (Fu) EU RESTRICTED 16822/EPCO/BVL/04 rev. 1-0 (02.02.05) List of representative uses evaluated

List of representative uses evaluated*


(a)

Member State

or Country

Product name

F G or I

(b)

Pests or Group of

pests controlled

(c)

Formulation

Application


PHI (days)

(l)

Remarks:

(m) Type Conc.

(d-f)

of as

(i)

method kind

(f-h)


(j)

number min max

(k)

interval between

applications (min)

kg as/hl

min max

water l/ha

min max

kg as/ha

min max

Cereals


BAS

560 00 F

F


SC

300 g/L

over plant spray

30 – 79

1 – 2

21

0.150

100-400

0.15–0.038

35

Cereals


BAS

560 00 F

F


SC

300 g/L

over plant spray

30 – 35

1

-

0.150

100-400

0.15-0.038

-

Grapevines

Northern Europe

BAS

560 02 F

F


SC

500 g/L

over plant spray

15 – 81

1 – 8

12

0.1

1000

0.010

28

Grapevines

Southern Europe

BAS

560 02 F

F


SC

500 g/L

over plant spray

57 – 81

1 – 8

12

0.1

1000

0.010

28



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EPCO Expert Meeting 18 (21 – 25 February 2005) 17274/EPCO/BVL/05 Metrafenone 21 February 2005

REPORT OF EPCO EXPERT MEETING 18 METRAFENONE Rapporteur Member State: The United Kingdom

Specific comments on the active substance in the section 2. Mammalian Toxicology are already listed in the relevant reporting table. Comments submitted for this meeting are listed below. 1. Comments submitted for this meeting:

Date Supplier File Name none Name


Date Supplier File Name 09 June 2004 RMS/United Kingdom Metrafenone consultation report 14 July 2004 RMS/United Kingdom Metrafenone reporting table rev1-1 25 November 2004 RMS/United Kingdom Metrafenone list of end points 25 November 2004 RMS/United Kingdom Metrafenone evaluation table rev0-1November 2004 RMS/United Kingdom Metrafenone addendum 1 December 2004 RMS/United Kingdom Metrafenone list of essential studies20 January 2005 RMS/United Kingdom Metrafenone metabolites table

3. Documents tabled at the meeting:

Date Supplier File Name none Name

The conclusions of the meeting were as follows: 4. Data on preparations: It is a new active substance and a completeness check has

been submitted. Data on two formulations have been submitted. 5. Classification and labelling: No classification and labelling has been proposed for the

active 6. Recommended restrictions/conditions for use: None proposed 7. Reference List

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Areas of concern: none proposed Appendix 1: EPCO discussion table: METRAFENONE


EPCO Expert Meeting 18 (21 – 25 February 2004) 17274/EPCO/BVL/05 Metrafenone 21 February 2005 Appendix 1: Discussion Table, Metrafenone (Fu) 2. Mammalian Toxicology No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert

Meeting

Open point 2.1 A proposal for the classification and labelling (category 3 and labelling with Xn, R40) of the active substance to be discussed at an expert meeting. Refer to reporting table 2(2) See also points 2(3), 2(4), 2(5), 2(9), 2(14)

A statement has been submitted by the notifier, which supports non-classification. The liver tumours were only seen in groups receiving high dietary concentrations of metrafenone given over a long duration. A mode of action has been proposed by the notifier (summary in the addendum) for these liver tumours following the “IPCS Conceptual Framework for Evaluating a Mode of Action for Chemical Carcinogens” as recently described. . The tumours have been observed in rats and male mice at very high dose levels. The experts agree with the argumentation presented in the addendum. The relevance to humans is not seen. Therefore the proposal for classification R 40 is not supported

Open point fulfilled. The proposal for classification R40 is not supported for the active substance

Open point 2.2 On the basis of the agreed proposal for the classification and labeling of the active substance the preparations should be labeled accordingly. Refer to reporting table 2(5)

A proposal has only been made for the formulation BAS 560 00 F on the basis of the skin sensitising properties of a co-formulant. EPCO supports the proposal R 43.

Open point fulfilled. R43 has been proposed by EPCO 18 for the preparation BAS 560 00 F

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EPCO Expert Meeting 18 (21 – 25 February 2004) 17274/EPCO/BVL/05 Metrafenone 21 February 2005 No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert

Meeting

Open point 2.3. The classification of the active substance regarding to its teratogenic potential should be discussed at an expert meeting. Refer to reporting table 2(13)

No effects have been reported in rats. In rabbits, maternal toxicity including reduced food consumption and body weight loss has been observed prior abortion or premature delivery at 350 and 700 mg/kg bw/day. Therefore no classification and labelling regarding developmental toxicity has been proposed for the active substance.

Open point fulfilled. No classification regarding developmental toxicity has been proposed.

The long term AOEL should be deleted from the list of end points, because it is not needed for any calculations. The drinking water limit should also be deleted.

New open point: RMS to amend the list of end points with regard to the long term AOEL.

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Evaluation table, Metrafenone (Fu) EU RESTRICTED 16822/EPCO/BVL/04 rev. 1-0 (21.02.05) section 2 – Mammalian toxicology

Appendix 2: Evaluation table 2. Mammalian Toxicology No.




Column DRecommendations EPCO Expert Meeting / Conclusions of the Evaluation Meeting



Open point 2.1 A proposal for the classification and labelling (category 3 and labelling with Xn, R40) of the active substance to be discussed at an expert meeting. Refer to reporting table 2(2) See also points 2(3), 2(4), 2(5), 2(9), 2(14)

An information paper commenting upon the classification and labelling will be submitted by the notifier until 19 November 2004.

Classification and labelling to be discussed at the expert meeting, final decision rests with ECB. The addendum to the DAR contains the applicant’s case against classification with regard to carcinogenicity.

EPCO 18 (21.-25.02.2005): Open point fulfilled. The proposal for classification R40 is not supported for the active substance

Open point 2.2 On the basis of the agreed proposal for the classification and labeling of the active substance the preparations should be labeled accordingly. Refer to reporting table 2(5)

See open point 2.1. EPCO 18 (21.-25.02.2005): Open point fulfilled. R43 has been proposed by EPCO 18 for the preparation BAS 560 00 F

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EU RESTRICTED 16822/EPCO/BVL/04 rev. 1-0 (21.02.05) ction 2 – Mammalian toxicology

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Open point 2.3. The classification of the active substance regarding to its teratogenic potential should be discussed at an expert meeting. Refer to reporting table 2(13)

The RMS does not consider that there is evidence of teratogenicity in either developmental study. To be discussed at expert meeting and finally determined by ECB.

EPCO 18 (21.-25.02.2005): Open point fulfilled. No classification regarding developmental toxicity has been proposed.

New open point 2.4: RMS to amend the list of end points with regard to the long term AOEL.

EPCO 18 (21.-25.02.2005): Open point still open.

Evaluation table, Metrafenone (Fu)se

No.


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REPORT OF EPCO EXPERT MEETING 19 METRAFENONE Rapporteur Member State: The United Kingdom Specific comments on the active substance in the section 3. Residues are already listed in the relevant reporting table. Comments submitted for this meeting are listed below. 1. Comments submitted for this meeting:



Date Supplier File Name 25 November 2004 RMS/United Kingdom Metrafenone list of end points December 2004 RMS/United Kingdom Metrafenone list of essential studies



The conclusions of the meeting were as follows: 4. Data on preparations: Complete. 5. Classification and labelling: No discussion needed. 6. Recommended restrictions/conditions for use: None 7. Reference List Areas of concern: None

Appendix 1: EPCO discussion table: METRAFENONE


EPCO Expert Meeting 19 (23 – 25 February 2005) 17281/EPCO/BVL/05 Metrafenone 23 February 2005 Appendix 1: Discussion Table, Metrafenone (Fu) 3. Residues No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert

Meeting

RMS gave a brief introduction on the substance. No need for a refined risk assessment was seen. No need for residue definition in animals due to the fact that the uses trigger no significant intakes in animals. EFSA notes that the predicted exposure of livestock is above the trigger for conducting metabolism studies in animals. Therefore a residue definition for animal products should be proposed as outcome of these studies.

EPCO 19 (23.-25.03.2005) Data complete

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Evaluation table, Metrafenone (Fu) EU RESTRICTED 16822/EPCO/BVL/04 rev. 1-0 (23.02.05) section 3 – Residues

Appendix 2: Evaluation table 3. Residues No.





Section 3Data requirements: - Open points: -

Section 3Data requirements: - Open points: - Data gaps: -

EPCO 19 (23.-25.03.2005) Data complete No need for residue definition in animals due to the fact that the uses trigger no significant intakes in animals. EFSA notes that the predicted exposure of livestock is above the trigger for conducting metabolism studies in animals. Therefore a residue definition for animal products should be proposed as outcome of these studies.

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EU RESTRICTED 16822/EPCO/BVL/04 rev. 1-0 (23.02.05) resentative uses evaluated

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List of representative uses evaluated*


(a)

Member State

or Country

Product name

F G or I

(b)

Pests or Group of

pests controlled

(c)

Formulation

Application


PHI (days)

(l)

Remarks:

(m) Type Conc.

(d-f)

of as

(i)

method kind

(f-h)


(j)

number min max

(k)

interval between

applications (min)

kg as/hl

min max

water l/ha

min max

kg as/ha

min max

Cereals


BAS

560 00 F

F


SC

300 g/L

over plant spray

30 – 79

1 – 2

21

0.150

100-400

0.15–0.038

35

Cereals


BAS

560 00 F

F


SC

300 g/L

over plant spray

30 – 35

1

-

0.150

100-400

0.15-0.038

-

Grapevines

Northern Europe

BAS

560 02 F

F


SC

500 g/L

over plant spray

15 – 81

1 – 8

12

0.1

1000

0.010

28

Grapevines

Southern Europe

BAS

560 02 F

F


SC

500 g/L

over plant spray

57 – 81

1 – 8

12

0.1

1000

0.010

28



Evaluation table, Metrafenone (Fu)List of rep

EPCO Expert Meeting 20 (01 – 03 March 2005) 17385/EPCO/BVL/05 Metrafenone 01 March 2005

REPORT OF EPCO EXPERT MEETING 20 METRAFENONE Rapporteur Member State: The United Kingdom Specific comments on the active substance in the section 1. Physical and Chemical Properties are already listed in the relevant reporting table. Comments submitted for this meeting are listed below. 1. Comments submitted for this meeting:

Date Supplier File Name none


Date Supplier File Name November 2004 RMS/The United

Kingdom Metrafenone addendum 1 (Nov2004)

09 June 2004 RMS/The United Kingdom

Metrafenone consultation report (09-06-2004)

25 November 2004 RMS/The United Kingdom

Metrafenone evaluation table rev0-1 (25-11-2004)

25 November 2004 RMS/The United Kingdom

Metrafenone list of end points (25-11-2004)

December 2004 RMS/The United Kingdom

Metrafenone list of essential studies (Dec2004)_all_sections

20 January 2005 RMS/The United Kingdom

Metrafenone Metabolites 2005-01-20

14 July 2004 RMS/The United Kingdom

Metrafenone reporting table rev1-1 (14-07-2004)


Date Supplier File Name none

The conclusions of the meeting were as follows: 4. Data on preparations: BAS 560 00 F and BAS 560 02 F. 5. Classification and labelling: not discussed. 6. Recommended restrictions/conditions for use: none.

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EPCO Expert Meeting 20 (01 – 03 March 2005) 17385/EPCO/BVL/05 Metrafenone 01 March 2005

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Areas of concern: none Appendix 1: EPCO discussion table: METRAFENONE

Appendix 2: Evaluation table: METRAFENONE

EPCO Expert Meeting 20 (01 – 03 March 2005) 17385/EPCO/BVL/05 Metrafenone 01 March 2005 Appendix 1: Discussion Table, Metrafenone (Fu) 1. Physical and Chemical Properties No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert

Meeting

Open point 1.1 RMS should amend list of endpoints with the phrase “Analytical methods not required” concerning the analytical method for food of animal origin Refer to reporting table 1(7)

The RMS explained that methods are available and therefore the list of end points was amended accordingly. The experts agreed.

Open point fulfilled. The list of end points was amended.

1.1 Applicant to confirm shear rate associated with measurement on viscosity for both preparations (BAS 560 00 F and BAS 560 02 F). Refer to reporting table 1(12)

The RMS explained that the data were submitted. The evaluation is presented in the addendum 1 (page 4). The experts agreed.

Data requirement fulfilled. The data were submitted and the evaluation presented in an addendum.

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EPCO Expert Meeting 20 (01 – 03 March 2005) 17385/EPCO/BVL/05 Metrafenone 01 March 2005 No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert

Meeting

Open point 1.2 RMS to provide an addendum concerning information chromatograms for the analytical method for food of animal origin. Refer to reporting table 1(16)

The RMS explained that a paragraph in the addendum makes the information clear now. The situation was that additional information had to be gained from the company by personal communication and was not submitted with the original dossier. The experts agreed.

Open point fulfilled. The RMS provided an addendum which clarified that the information was not part of the original dossier.

Open point 1.3 RMS to amend the list of endpoints concerning the residue definition and to consider in an addendum to the draft assessment report. Residue definition has to be confirmed by experts meetings (fate and behaviour and, if appropriate, ecotox and tox). Refer to reporting table 1(18)

The meeting got the message that the metabolite CL 3770160 is neither of toxicological nor of ecotoxicological relevance. The meeting therefore took note that the residue definition is just metrafenone.

Open point fulfilled. The meeting took note that the residue definition is just metrafenone.

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Meeting

Open point 1.4 RMS to amend the list of endpoints concerning the validated commodity (enforcement method for food of plant origin) Refer to reporting table 1(6)

RMS amended the list of end points. NL is the opinion that the amendment is too general. The meeting clarified that only wine can be meant by “all other plant commodities”. RMS will change it in the list of end points (see new open point 1.5).

Open point fulfilled. The list of end points was amended.

Comment from DE raised at the meeting: The statement regarding the method of Pelz & Steinhauer (2001b) to present acceptable chromatogramms for confirmation (3 ions) is incorrect.

The experts took note of this comment, but agreed that there is no need for further action since an analytical method for the food of animal origin is not required (no residue definition).

Comment addressed.

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Meeting

Comment from DE raised at the meeting: From the statement “Acceptable data was presented for all aspects of validation.” it may be concluded, that confirmatory method is fully validated. From our point of view not sufficient number of quantitative data is presented.

The experts took note of this comment, but agreed that there is no need for further action since an analytical method for the food of animal origin is not required (no residue definition).

Comment addressed.

Comment from DE raised at the meeting: DAR should contain the information, that confirmatory methods of analysis for residues in soil, water and air are proposed but not validated.

The experts agreed that a new data gap could be identified unless sufficient data concerning the mass spectra are available (soil method). RMS will check and clarify this. Therefore a new open point was set. A HPLC-MS method was used as the primary analysis method for water. Although this did not use 3 ions of m/z >100 (as recommended by SANCO/825/00), MS/MS confirmatory ions were also demonstrated and the experts agreed that the combined information was sufficient. The experts do not see a need to required further data for the air method.

The experts agreed to set a new open point 1.5: RMS to clarify whether or not sufficient information with respect to the mass spectrum is available to accept the submitted analytical method without further validation (for confirmatory purposes).

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Meeting

New open point 1.5: RMS to clarify whether or not sufficient information with respect to the mass spectrum is available to accept the submitted analytical method without further validation (for confirmatory purposes).

This open point was proposed at EPCO 20. Open point still open.


The list of end points was revised in the meeting and the following amendments were proposed: Dissociation constant: the entry should be “no dissociation” Classification and proposed labelling: the entry for the plant protection product should be deleted as it is list of end points for active substance and not for the formulation. The list should be revised so that it follows the template given in EPCO manual E4, i.e. the table “Summary of uses supported by available data „ should be replaced by the table “List of representative uses evaluated” as included at the end of the evaluation table; also name of the active substance should be included in the brackets. The term all other plant commodities should be replaced by wine in the box "Food/feed of plant origin”.

Open point still open.

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Evaluation table, Metrafenone (Fu) EU RESTRICTED 16822/EPCO/BVL/04 rev. 1-0 (01.03.05) section 1 – Identity, Physical and chemical properties, Details of uses and further information, Methods of analysis

Appendix 2: Evaluation table 1. Identity, Physical and chemical properties, Details of uses and further information, Methods of analysis No.






Section 1Data gaps: - Open points: 2

Open point 1.1 RMS should amend list of endpoints with the phrase “Analytical methods not required” concerning the analytical method for food of animal origin Refer to reporting table 1(7)

The list of endpoints has been amended.

EPCO 20 (01. – 03.03.2005): Open point fulfilled. The list of end points was amended.

1.1 Applicant to confirm shear rate associated with measurement on viscosity for both preparations (BAS 560 00 F and BAS 560 02 F). Refer to reporting table 1(12)

Information regarding shear rate was submitted in June 2004.

The shear rate confirmed for both preparations is 100 s-1, for full details see addendum.

EPCO 20 (01. – 03.03.2005): Data requirement fulfilled. The data were submitted and the evaluation presented in an addendum.

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No.





Open point 1.2 RMS to provide an addendum concerning information chromatograms for the analytical method for food of animal origin. Refer to reporting table 1(16)

See addendum. Currently, the DAR implies that all chromatograms were supplied in the report of Pelz & Steinhauer (2001b); in fact chromatograms for confirmatory ions were obtained via correspondence with the applicant. The same clarification is required for sections of the DAR dealing with validation of method DFG S19 for citrus, oilseed rape, barley grain, grapes and wine: chromatograms not present in the original reports were obtained by correspondence with the applicant.

EPCO 20 (01. – 03.03.2005): Open point fulfilled. The RMS provided an addendum which clarified that the information was not part of the original dossier.

Open point 1.3 RMS to amend the list of endpoints concerning the residue definition and to consider in an addendum to the draft assessment report. Residue definition has to be confirmed by experts meetings (fate and behaviour and, if appropriate, ecotox and tox). Refer to reporting table 1(18)

The endpoints list has been amended to delete CL 377160. The Rapporteur’s opinion is that CL 377160 is not relevant and does not need to be included in the residue definition Residue definition to be confirmed following discussion at the expert meetings.

EPCO 20 (01. – 03.03.2005): Open point fulfilled. The meeting took note that the residue definition is just metrafenone.

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No.





Open point 1.4 RMS to amend the list of endpoints concerning the validated commodity (enforcement method for food of plant origin) Refer to reporting table 1(6)

The list of endpoints has been amended.

EPCO 20 (01. – 03.03.2005): Open point fulfilled. The list of end points was amended.

Comment from DE raised at the EPCO 20 meeting: The statement regarding the method of Pelz & Steinhauer (2001b) to present acceptable chromatogramms for confirmation (3 ions) is incorrect.

EPCO 20 (01. – 03.03.2005): Comment addressed. The experts took note of this comment, but agreed that there is no need for further action since an analytical method for the food of animal origin is not required (no residue definition).

Comment from DE raised at the EPCO 20 meeting: From the statement “Acceptable data was presented for all aspects of validation.” it may be concluded, that confirmatory method is fully validated. From our point of view not sufficient number of quantitative data is presented.

EPCO 20 (01. – 03.03.2005): Comment addressed. The experts took note of this comment, but agreed that there is no need for further action since an analytical method for the food of animal origin is not required (no residue definition).

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No.





Comment from DE raised at the EPCO 20 meeting: DAR should contain the information, that confirmatory methods of analysis for residues in soil, water and air are proposed but not validated.

EPCO 20 (01. – 03.03.2005): The experts agreed that a new data gap could be identified unless sufficient data concerning the mass spectra are available (soil method). Therefore the experts agreed to set a new open point 1.5.

New open point 1.5: RMS to clarify whether or not sufficient information with respect to the mass spectrum is available to accept the submitted analytical method without further validation (for confirmatory purposes). This open point was proposed at EPCO 20.

EPCO 20 (01. – 03.03.2005): Open point still open.


EPCO 20 (01. – 03.03.2005): Open point still open.

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PEER REVIEW REPORT ON METRAFENONE 16.01.2006 TABLE OF … · PEER REVIEW REPORT ON METRAFENONE...

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