PEER REVIEW REPORT ON TRIFLURALIN 04.04.2005 TABLE OF CONTENTS · PEER REVIEW REPORT ON TRIFLURALIN...

PEER REVIEW REPORT ON TRIFLURALIN 04.04.2005 TABLE OF CONTENTS Document File Name 00 Cover page 00 trifluralin.cover.doc 01 All comments received on the DAR 01 trifluralin all comments.doc 02 Reporting table all sections 02 trifluralin rep table rev1-1.doc 03 All reports from EPCO Expert Meetings 03 trifluralin all reports.doc 04 Evaluation table 04 trifluralin eval table rev3-1.doc List of all reports from EPCO Expert Meetings Date Name Section 27.-28.04.2004 EPCO Expert Meeting 02 Environmental Fate and Behaviour 28.-29.04.2004 EPCO Expert Meeting 03 Ecotoxicology 10.-12.05.2004 EPCO Expert Meeting 04 Mammalian toxicology 11.-12.05.2004 EPCO Expert Meeting 05 Residues and Analytical Methods 15.-16.06.2004 EPCO Expert Meeting 06 Physical and Chemical Properties 22.-22.06.2004 EPCO Expert Meeting 08 Ecotoxicology

1/130

REPORT OF EPCO EXPERT MEETING TRIFLURALIN Rapporteur Member State: GREECE Specific comments on the active substance in the section 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 this meeting:

Date Supplier File Name 22 December 2004 RMS/Greece Trifluralin consultation report 29 March 2004 RMS/Greece Trifluralin end points 04 February 2004 RMS/Greece Trifluralin reporting table rev1-1 29 March 2004 RMS/Greece Trifluralin evaluation table rev0-1 3. Documents tabled at the meeting:

None The conclusions of the meeting were as follows: 3. Data on preparations: Considered complete 4. Classification and labelling: RMS proposes possible candidate for R53. Ecotox to

confirm. 5. Recommended restrictions/conditions for use: Consider restricting uses to soil

incorporated uses only to reduce potential for volatilisation. Areas of concern: Possible candidate for PBT classification. The meeting noted the possible issue of volatilisation, but also noted that no harmonised scheme to calculate PECair was available at the time of evaluation and no estimate was provided by the Notifier. PECair and contamination of other compartments via air may be considered further at MS level (this was identified during this meeting – other areas of concern may already have been identified in the DAR) Appendix 1: EPCO discussion table: TRIFLURALIN Appendix 2: Evaluation Table

EPCO Expert Meeting 02 18000/EPCO/PSD/04 Trifluralin 03 May 2004

2/130

Appendix 1: Discussion Table, Trifluralin (Hb) 4. Environmental Fate and Behaviour No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert

Meeting

Open point 4.1: The ecotoxicological risk assessment of metabolites TR-6 and TR-15 should be confirmed in the expert meeting (ecotoxicology).

RMS: detailed discussion had taken place between Notifier and MS regarding the relevance of these photoproducts. RMS considered these should be evaluated at MS level. EFSA recommended discusion in the expert meeting. Chair: confirmed that if these products were only formed in the aqueous photolysis study then based on previous ECCO meetings such metabolites should be dealt with at MS level. DE: Questioned whether these metabolites were present in the natural water photolysis study. RMS: Study quality was questionable. Although the study is more representative, it did not comply with guidelines, hence relied on aqueous photolysis study. Presence of photosensitisers in natural water systems may have influenced half lives. DE: Suggested the need for a sediment water study in the presence of light should be decided at MS level. NL: Agree with DE. Aquatic guidance document is not clear on how to assess photolysis metabolites. PL: TR-6 is an analogue of nitroanaline – which may be concern with regards ecotoxicity. UK: Questioned whether risk assessment should be based on PEC provided, or left to MS level during National assessment. DE: Did not agree with PEC calculated. Percentages of formation should be taken from photolysis study as a worst case and base risk assessment on these values. RMS: Notifier argued that Trifluralin partitioned to sediment rapidly and reduced scope for photolysis. Water sediment and photolysis studies were combined to provide a best estimate for PEC values. SE: Percentage values taken from water sediment study were based on sediment spiking study. PEC should not be based on this and agree with DE concerns.

EPCO 2 (27.-28.04.2004): Meeting determined revised PEC values based on worst case percentage formation rates for TR-6 and TR-15. Data requirement 4.4: The requirement for a sediment water study to be conducted in the presence of light to be decided at MS level (following a preliminary risk assessment based on revised PEC values provided). Data requirement to be dealt with at Member State Level. Ecotox to confirm the acceptability or not of TR-6 and TR-15 in surface waters at the revised PEC values. Ecotox to note TR-6 may be persistent in aquatic systems and the possible need for


3/130

No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert Meeting

UK: Rapid partitioning, therefore extremely rapid photolysis would be needed to get the same levels of metabolites as in the aqueous photolysis study. Should be possible to calculate a worst case value based on the photolysis study percentages. Questioned whether the RMS approach was too conservative. SE: Partitioning was not always so rapid in all systems tested, so choice of study was important. DE: with no information on a light water sediment system, the highest values should be taken as worst case. UK: Agreed to take the worst case precentage formation. RMS: Water sediment study included aeration of water phase, and it was proposed that high losses occurred due to volatilisation. Chair concluded that the PECs provided could not be agreed for use in ecotox assessments. RMS: Confirmed that for each photoproduct PECs would be now based on the maximum percentage formation rates. This would be more worst case than those currently presented. UK: Revised PECs are as follows:- 1m buffer zone – TR-6 = 5.6ug/l; TR-15 = 3.49ug/l 5m buffer zone – TR-6 = 1.15ug/l; TR-15 = 0.72ug/l 10m buffer zone – TR-6 = 0.58 ug/l; TR-15 = 0.36ug/l Chair concluded that the revised PECs above would be provided to the ecotox meeting to enable a risk assesmment to be conducted. RMS: Will update the endpoints sheet accordingly with the conclusions of the meeting.

chronic toxicity data. Open point 4.4: RMS to amend the list of end points with regard to the PEC values for water. This new open point was proposed at the meeting: Open point still open


4/130


Open point 4.2: Data requirements for anaerobic metabolite TR-4 to be confirmed in an expert meeting

RMS: No major metabolites formed in aerobic soil study. TR-4 formed under anaerobic soil conditions, and the rate of degradation of the parent compound in soil was noted to be faster under anaerobic conditions compared with aerobic conditions. RMS asked for views of MS where anaerobic conditions are more prevalent. RMS wanted confirmation of possible ecotoxicity of TR-4 by an expert meeting, and requested views of Northern MS and advice on dealing with anaerobic metabolites. PL: Aerobic degradation of TR-4 can be deduced since structure is similar to parent (only difference is additional nitro group) and cleavage position can be predicted. Pathway would be similar to TR-2 and possibly TR-20 and TR-25. CZ: TR-4 is similar to TR-5, and under aerobic degradation no further metabolites were specified. UK: UK would want risk assessment for TR-4, since trifluralin is persistent and in heavy soils there will be exposure to anaerobic conditions. Do not think there is a risk of contamination to groundwater. Although we can surmise an aerobic degradation pathway, no evidence in the package that any of the metabolites or parent are particularly rapidly degraded. Chair: Under ECCO, anaerobic metabolite issue was left to MS to resolve. Autumn/Winter applications – northern MS considered anaerobic conditions present, but if rapid degradation of anaerobic metabolites under aerobic conditions occurred, there was generally less concern over their effects. NL: Agree that these metabolites may be considered at MS level. PL: Agree also.

EPCO 2 (27.-28.04.2004): Open point fulfilled. No further data required for TR-4 at EU level. Data requirement 4.5: Data for the anaerobic metabolite TR-4 are required if anaerobic conditions are important for crops specified. Data requirement to be dealt with at Member State Level.

Open point 4.3: DT50 values of the water phase and the whole system in the water/ sediment system need to be discussed in an expert meeting.

SE: Requested clarification of DT50 to be used in aquatic risk assessment. RMS: Suggested use of the worst case value available i.e. 13 d in this case (from 1st study) rather than 1-2 d from third study. Third study is most reliable, however PECs are based on first study as worst case and on a mean value as a refined figure. Issue to be dealt with further by ecotox. UK: Ecotox triggers normally based on water spiked studies (e.g. first study), ie a dissipation half life, so maybe the first study value (13 d) should be used. Two i th t t i d th PEC l

EPCO 2 (27.-28.04.2004): Open point fulfilled. Meeting proposed the use of a 13d DT50 in a worst case first tier PEC assessment. Further refinement of PECs based on


5/130


issues: the ecotox trigger and the PEC value. SE: Queried use of 6h DT50 for the fish risk assessment. Should take value of 1-2 days from third study (or 13 d from 1st study) but not 6h. DE: Agree with the use of a 13 d DT50 in the assessment. A 2d DT50 may be more realistic based on previous discussions regarding photolysis. RMS: First tier assessment based on 13d, and a further refinement has been included based on a 1 d DT50 and included in the revised endpoint sheet. A further assessment based on a DT50 of 2d will be included. SE: Agreed to the replacement of the refined PECsw based on 1d with new data based on 2d. Chair: Confirmed that the refined PECsw should be based on a realistic worst case value of 2d, rather than 1d. First tier assessment should be based on 13 d as already supplied. Confirmed that a 6h DT50 should not be used as part of the chronic risk assessment. RMS: Whole system DT50 not provided for the third study in the endpoints sheet. Correct values will be added. Whole system DT50 values are confirmed to be 6 and 15 d assuming first order kinetics.

a realistic worst case DT50 of 2d may be considered following evaluation of worst case PECs by ecotox. Open point 4.5: RMS to update the list of end points with a refined PECsw based on a DT50 of 2 d (replacing values for a DT50 of 1 d). This new open point was proposed at the meeting. Open point still open Open point 4.6: RMS to update the list of end points with whole system DT50 value for third study. This new open point was proposed at the meeting. Open point still open


6/130


4.1 Notifier to submit for TR-4 a complete set of FOCUS scenarios for the representative uses (oilseed rape, sunflower, cotton).

RMS: Has evaluated submitted study in addenda and considers this acceptable. TR-4 does not appear to contaminate groundwater based on worst case assumptions. RMS confirms that risk of groundwater contamination from TR-4 to be considered further at MS level. DE: Suggest endpoint sheet be amended to read <0.001ug/l.

EPCO 2 (27.-28.04.2004): Data requirement 4.1. Risk of groundwater contamination from anaerobic metabolite TR-4 to be considered further at MS level if necessary. Data requirement to be dealt with at Member State Level.

4.2 Notifier to identify non-identified substances in the water/sediment study or to submit a new water/sediment study.

Chair: Notifier submitted new third water sediment study (2 already submitted), evaluated by RMS and included in addenda and considered acceptable. RMS satisfied. Non-identifed substances were identified in new study – TR-4, TR-7 and TR-14 all major in sediment. DE: 20% still unidentified. RMS: Confirmed this, and believed this acceptable compared with previous studies. Chair: Confirmed all individual components present at <5%. DE: Satisfied by new study. Chair: Meeting agrees that new (third) water sediment study is of sufficient quality and data requirement fulfilled.

EPCO 2 (27.-28.04.2004): Data requirement fulfilled.


7/130


4.3 Initial PECsediment for the metabolites TR-4, TR-7 and TR-14 are required, AIII 9.2.3, (this requirement was added by the RMS after the submission of new data from the notifier (new water/sediment study study no. 030067, February 2004)

NL: Requested addition of PECsw calculated assuming drift at 1m DE: Queried the default sediment depth of 5cm – based on high Koc for Trifluralin and metabolites, may be more reasonable to consider a depth of 1-2cm? Chair: Previous assessments always based on 5cm. PL: Consideration of a 2cm depth would be unrealistic as these surface layers are prone to re-suspension following disturbance. NL: Queried the use of a bulk density of 1.5g/cm3. DE: Agreed this figure should be 1.3g/cm3 (based on solid phase representing a fraction of 0.8 and aqueous phase representing 0.2 of sediment). CZ: Queried the value of 0.8g/cm3 taken from FOCUS model and whether this value could be used outside of the FOCUS model approach. UK: Clarified that FOCUS calculates PECsed on a dry weight basis. Chair: Sediment depth of 5cm and bulk density of 1.3g/cm3 should be maintained for an EU level assessment. The meeting notes that metabolite TR-14, and to a lesser extent TR-4, are persistent and should be considered further by ecotox meeting if needed.

EPCO 2 (27.-28.04.2004): Data requirement fulfilled. The meeting notes that metabolite TR-14, and to a lesser extent TR-4, are persistent and should be considered further by ecotox meeting if needed. Open point 4.7: RMS to re-calculate sediment PECs based on a bulk density of 1.3g/cm3 if original values based on a value of 1.5 g/cm3 (for Parent AND metabolites). If values based on a figure of 0.8g/cm3, the meeting accepts the values provided (RMS to first check bulk density used in original PECsed values and ensure consistency between addenda and endpoints sheet). PECsw/PECsed values for 1m to be added in list of endpoints.


8/130


SE commented that the persistence and bioaccumulation potential of the substance make it unnacceptable

SE: Trifluralin is a PBT substance and also identified in monitoring studies (Mar. Poll. Bull., Vol. 32 pp410-419, 1996) and identified in an OSPAR background document (Draft OSPAR Background Document on Hazardous Substances Identified for Priority Action – Trifluralin, 19-23 April, 2004) RMS: Commission document (Background Document on Recommendations for the Review of 14 Priority Hazardous Substances – Brussels, 26 Oct, 2003, EAF(6) – 05/02 – PHS review complete reports) suggests Trifluralin does not match the PBT criteria because environmental persistence values do not meet the trigger values (based on aquatic trigger values) DE: Believes the PBT criteria are fulfilled for trifluralin, but POP criteria may not be fulfilled due to short half life in air UK: B and T criteria are not to be decided by this meeting, and we can only agree that the Persistence criteria are met.

EPCO 2 (27.-28.04.2004): Point fulfilled.

RMS: Confirmed applications in winter cereals are made post-sowing (with no soil incorporation)

SE/NL: Risk to grazing birds may need to be assessed following post-sowing uses on winter cereals. RMS: Confirmed applications are made post-sowing in winter cereals. UK: confirmed applications are made post-sowing and up to the three leaf stage in winter cereals. RMS: Confirmed the uses listed are those evaluated at EU level.

EPCO 2 (27.-28.04.2004): Ecotox meeting to note post-emergent applications to winter cereals and possible issue of risk to grazing birds.


9/130


SE: Queried location of US field trial sites

SE: Requested location of US field trials be added to the endpoints sheet, particularly as DT50 values are significantly shorter in these studies. RMS: Confirmed states were California, Illinois and Georgia – i.e. some southern and some northern. EU trials were of comparable conditions, therefore US data accepted. NL/SE: queried the calculation of a mean value based on combined data for N and S areas. CZ: Did not consider it possible to just accept data from US sites. Must be based on a consideration of temperature and soil types for example. RMS: Some US field data excluded since studies based on non-representative formulations.

EPCO 2 (27.-28.04.2004): Open point 4.8: RMS top add State where US field dissipation trials were conducted. This new open point was proposed at the meeting. Open point still open

UK: Query re soil accumulation

UK: Soil accumulation study demonstrates that at that site no accumulation occurred. But dissipation at that site was noted to be in the middle of the range of dissipation rates for Trifluralin. Possible need for a data requirement for a calculation of accumulation taking into account longer dissipation rates from other sites. RMS: Proposed this be dealt with at MS level where accumulation may be an issue. UK: DT90 > 1 year are available. Notifier should be asked to address the situation where longer dissipation rates occur via a calculation of a maximum plateau concentration. PL: If accumulation exceeds the sorption capacity of the soil, groundwater contamination may be an issue. EFSA: A safe use is identified based on the accumulation study, therefore the assessment of accumulation may be made at MS level for situations where the half life is considered to be longer. RMS: Agree with proposal of EFSA to consider accumulation as a MS issue where safe use identified by accumulation study. Chair: Confirmed this is normally dealt with at EU level, and thought a basic calculation of accumulation should still be included for assessment at EU level.

EPCO 2 (27.-28.04.2004): Point still open Data requirement 4.6: A calculation of maximum plateau concentration in soil based on the longest field dissipation rate (ie DT50 = 375d) should be included. Data requirement essential for unconditional Annex I inclusion. UK: Plateau residue concentration immediately before the following years


10/130


Implications of the assessment of the maximum plateau PECsoil can be made further at MS level.

application = 1.66 mg/kg. Maximum PECsoil after subsequent application = 3.26mg/kg (reached after approx. 13 years continuous application based on 1st order DT50 of 375d, assuming no interception and even distribution in a 5cm soil layer and bulk density of 1.5g/cm3). Ecotox to consider these revised values in their assessment. Ecotox will need to consider any higher PECsoil value submitted.


11/130


DE: Query re volatility and need to reassess with FOCUSair as soon as possible

DE: Volatilisation may be an issue when any future FOCUSair report guidance would be applied and Trifluralin should be re-evaluated when final guidance available. EFSA: Should not re-assess actives, only during the 10 year review process as laid down in the Directive. Decisions should be based on the science available at the time of the assessment. DE: Remarks included by Commission for the active substance Pendimethalin that it should be reassessed according to FOCUS, therefore same rules may apply here? RMS: Notifier refused to provide PECair values since no harmonised guidance available. DE: Provision of PECair estimates may result in the decision for non-inclusion in Annex I, since mitigation measures are much more difficult for the air compartment. RMS: Confirmed the calculated half life in air was 5.3 h. DE: Trifluralin would be predicted to be deposited in surface waters or on soil (for example) more rapidly than 5 h, therefore the half life proposed is not relevant in this case. EFSA: Commented on incorporated uses and the evidence that volatilisation from such uses was much lower than applications to the soil surface. This information has not been considered further in this meeting although it may be used to mitigate concerns over contamination of air from such uses.

EPCO 2 (27.-28.04.2004): Point fulfilled Discussion held to provide background to The Areas of Concern Box (see p1). PECair and contamination of other compartments via air may be considered at MS level

Evaluation table Trifluralin (Hb) EU RESTRICTED 16395/EPCO/BVL/04 rev. 0-3 (03.05.04) section 4 - Environmental Fate and Behaviour

12/130

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 D Recommendations EPCO Expert Meeting / Conclusions of the evaluation group

Section 4 Data requirements: 4 Open points: 4

Open point 4.1: The ecotoxicological risk assessment of metabolites TR-6 and TR-15 should be confirmed in the expert meeting (ecotoxicology). (Open point proposed at EPCO 2)

Based on the new EU water/sediment study (Ref. K63) and the amounts of TR-6 and TR-15 formed by photolysis, it is estimated that these photoproducts will be formed at 9.6% and 6.0% AR, respectively (see PEC calculations, March 2004). In terms of the amounts formed, these two photoproducts should not be considered relevant to surface water. Furthermore, PECsw values have been derived using a no-spray zone of 5 m since this gives a minimum acceptable level of safety for trifluralin. A further calculation was conducted assuming a 10 m no-spray zone (see PEC calculations, March 2004). The maximum PECsw for TR-6 was 0.14 µg/L (5 m) or 0.07 µg/L (10 m).

Initial PECsw values for the photoproducts TR-6 and TR-15 have been calculated by the notifier (March 2004). The assessment of this calculation is included in the Addendum under point B.8.6. An estimate of the exposure levels was made by multiplying the maximum photolysis amounts observed for TR-6 and TR-15 (50.4 and 31.5% AR) by the maximum amount of total radioactivity found in the water column from the new water/sediment study (study no. 030067, February 2004) excluding zero-time, 19% AR at 3 days. This gave reduced exposure levels of 9.6 and 6.0 % AR, respectively, for the calculation of PECsw values. Initial PECsw values for TR-6 were found to be 0.14 and 0.07 µg/l at 5

EPCO 2 (27.-28.04.2004): Meeting determined revised PEC values based on worst case percentage formation rates for TR-6 and TR-15. Ecotox to confirm the acceptability or not of TR-6 and TR-15 in surface waters at the revised PEC values. Ecotox to note TR-6 may be persistent in aquatic systems and the possible need for chronic toxicity data. Open point fulfilled, see new open point 4.4. and data requirement 4.3.


13/130

No.





Similarly for TR-15, the maximum PECsw was 0.11 µg/L (5 m) or 0.05 µg/L (10 m). In consideration of any surface water that might be consumed as drinking water, it is clear that these two photoproducts will likely not exceed 0.1 µg/L if a 10 m no-spray zone is maintained, or only just exceed 0.1 µg/L if a 5 m no-spray zone is maintained.

and 10 m buffer zones, respectively. Initial PECsw values for TR-15 were found to be 0.11 and 0.05 µg/kg at 5 and 10 m buffer zones, respectively. These new data are considered acceptable.

4.4 The requirement for a sediment water study to be conducted in the presence of light to be decided at MS level (following a preliminary risk assessment based on revised PEC values provided). This data requirement results from Open point 4.1 Data requirement to be dealt with at Member State Level.

EPCO 2 (27.-28.04.2004): Data requirement to be dealt with at Member State Level.


14/130

No.





Open point 4.4: RMS to amend the list of end points with regard to the PEC values for water. This new open point was proposed at the meeting: Open point still open

EPCO 2 (27.-28.04.2004): Open point still open

Open point 4.2: Data requirements for anaerobic metabolite TR-4 to be confirmed in an expert meeting

The FOCUS groundwater modelling (Ref. K64) showed that the PECgw was estimated to be 0.000 µg/L for all FOCUS scenarios relevant to the supported uses. This is the same as for parent compound and is indicative of their high Koc values. Since the PECgw for TR-4 was clearly < 0.1 µg/L, then this metabolite would not be considered relevant to groundwater, as prescribed in “Guidance Document on the Assessment of the Relevance of Metabolites in Groundwater of Substances Regulated Under Council Directive 91/414/EEC, Sanco/221/2000 – rev.10 –final; February 2003”. Therefore, any reference to assessing the biological or toxicological activity for TR-4 is not warranted.

The metabolite TR-4 was included in the definition of the residue because it was found to be major in soil under anaerobic conditions. The proposed definition of the residue in soil is not considered as final and it is up to the further evaluation. In addition, the RMS considers that more data should be provided for TR-4 in the case it is found to be biologically active. The RMS agrees that the data requirements for TR-4 should be confirmed in an expert meeting.

EPCO 2 (27.-28.04.2004): Open point fulfilled. No further data required for TR-4 at EU level. See new data requirement 4.4:


15/130

No.





4.5 Data for the anaerobic metabolite TR-4 are required if anaerobic conditions are important for crops specified. Data requirement to be dealt with at Member State Level.

EPCO 2 (27.-28.04.2004): Data requirement to be dealt with at Member State Level.

4.1 Notifier to submit for TR-4 a complete set of FOCUS scenarios for the representative uses (oilseed rape, sunflower, cotton).

A report (Ref. K64) has now been generated and has been submitted to the RMS together with these comments.

The modelling study “Reeves, G. (2004): Predicted environmental concentrations in groundwater for TR-4 (an anaerobic soil metabolite of trifluralin) according to the FOCUS scenarios. Dow AgroSciences, unpublished report no. GHE-P-10694 (1 March 2004). Ref. K64.” have been submitted to the RMS. The PECGW for the major anaerobic soil metabolite of trifluralin, i.e. TR-4, is estimated to be 0.000 µg/L for all FOCUS scenarios relevant to the supported uses. This study is considered acceptable.

EPCO 2 (27.-28.04.2004): Risk of groundwater contamination from anaerobic metabolite TR-4 to be considered further at MS level if necessary. Data requirement to be dealt with at Member State Level.


16/130

No.





4.2

Notifier to identify non-identified substances in the water/sediment study or to submit a new water/sediment study.

A report (Ref. K63) for a new water/sediment study has been submitted to the RMS.

A new water/sediment study has been submitted by the notifier (Cook W L., Meitl T. J., February 2004, study no. 030067). The assessment of this study is included in the Addendum under point B.8.4.3.2. Based on first-order degradation kinetics, the DT50 values for trifluralin in the water phase were 1 and 2 days for the French and English test systems, respectively. The DT50 values for trifluralin in the sediment layer were 15 and 7 days for the French and English test systems, respectively. The DT50 values for trifluralin in the whole system (both sediment and water) were 15 and 6 days for the French and English test systems, respectively. Three major metabolites were identified in the sediment layer, TR-4, TR-7 and TR-14. The metabolite TR-4 reached maximum concentrations in the sediment layer from 26 to 27% AR (at 17 and 7 days- data from two systems, the French and the English). The maximum concentrations of the metabolite TR-7 ranged from 5 to 14.2% AR at 33 days (data from two systems, th F h d th E li h) Th



17/130

No.





4.2

continued Notifier to identify non-identified substances in the water/sediment study or to submit a new water/sediment study.

the French and the English). The maximum concentrations of the metabolite TR-14 ranged from 21.2 to 29.5% AR at 54 days (data from two systems, the French and the English). The non-identified radiocarbon (NIR), which is the sum of multiple HPLC Peak areas (all less than 5% peak area), ranged from 0% to 23% AR. CO2 concentration was 0.4% AR for all samples. The non-extractable residues (NER) reached 77% AR at study termination. This study is considered acceptable.


18/130

No.





Open point 4.3: DT50 values of the water phase and the whole system in the water/ sediment system need to be discussed in an expert meeting.

We are prepared to discuss this issue with the RMS prior to the expert meeting Particular reference to the new water/sediment study will be made.

According to the new water/sediment study submitted (study no. 030067, February 2004) new DT50 values have been calculated for trifluralin ( in water phase, in sediment and in the whole system). The assessment of this study is included in the Addendum under point B.8.4.3.2 and is summarised in the Evaluation Table under point 4.2. All the DT50 values for trifluralin are now determined clearly and are considered reliable and acceptable.

EPCO 2 (27.-28.04.2004): Open point fulfilled. Meeting proposed the use of a 13d DT50 in a worst case first tier PEC assessment. Further refinement of PECs based on a realistic worst case DT50 of 2d may be considered following evaluation of worst case PECs by ecotox. Two new open points were proposed at the Expert Meeting (see open points 4.5. and 4.6).

Open point 4.5: RMS to update the list of end points with a refined PECsw based on a DT50 of 2 d (replacing values for a DT50 of 1 d). (This new open point was proposed at EPCO 2.)


19/130

No.





Open point 4.6: RMS to update the list of end points with whole system DT50 value for third study. (This new open point was proposed at EPCO 2.)

4.3 Initial PECsediment for the metabolites TR-4, TR-7 and TR-14 are required, AIII 9.2.3, (this requirement was added by the RMS after the submission of new data from the notifier (new water/sediment study study no. 030067, February 2004)

According to the new water/sediment study submitted (study no. 030067, February 2004) three major metabolites were identified in the sediment layer, TR-4, TR-7 and TR-14. Therefore, initial PECsediment values for the metabolites TR-4, TR-7 and TR-14 have been calculated by the notifier. The assessment of these calculations is included in the Addendum under point B.8.6. Initial PECsed for TR-4 were found to be 4.13 and 2.10 µg/kg at buffer zones of 5 and 10 m, respectively (maximum amount of TR-4 formed in sediment 26.5%). Initial PECsed for TR-7 were found to be 1.99 and 1.01 µg/kg at buffer zones of 5 and 10 m, respectively (maximum amount of TR-7 formed in sediment 14.2%).

EPCO 2 (27.-28.04.2004): Data requirement fulfilled. The meeting notes that metabolite TR-14, and to a lesser extent TR-4, are persistent and should be considered further by ecotox meeting if needed. A new open point was proposed at the Expert Meeting (see open point 4.7.)


20/130

No.





Initial PECsed for TR-14 were found to be 4.08 and 2.08 µg/kg at buffer zones of 5 and 10 m, respectively (maximum amount of TR-14 formed in sediment 29.5%). All the above PEC sediment values are considered reliable and acceptable.


21/130

No.





Open point 4.7: RMS to re-calculate sediment PECs based on a bulk density of 1.3g/cm3 if original values based on a value of 1.5 g/cm3 (for Parent AND metabolites). If values based on a figure of 0.8g/cm3, the meeting accepts the values provided (RMS to first check bulk density used in original PECsed values and ensure consistency between addenda and endpoints sheet). PECsw/PECsed values for 1m to be added to list of endpoints. (This new open point was proposed at EPCO 2.)



22/130

No.





Open point 4.8: RMS top add State where US field dissipation trials were conducted. (This new open point was proposed at EPCO 2.)


4.6 A calculation of maximum plateau concentration in soil based on the longest field dissipation rate (ie DT50 = 375d) should be included. (This new data requirement was proposed at EPCO 2)

EPCO 2 (27.-28.04.2004): Data requirement essential for unconditional Annex I inclusion.

EPCO Expert Meeting 03 (28 – 29 April 2004) 18001/EPCO/PSD/04 trifluralin 03 May 2004

23/130

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

None.


Date Supplier File Name 22 December 2003 RMS/Greece Trifluralin consultation report 09 January 2004 RMS/Greece Trifluralin end points 04 February 2004 RMS/Greece Trifluralin reporting table rev1-1 29 March 2004 RMS/Greece Trifluralin evaluation table rev0-1

3. Documents tabled at the meeting:

Date Supplier File Name 29 April 2004 RMS/Greece Revised Evaluation Table* * The meeting decided not to consider this document as there was no associated revised addendum and the issues require detailed consideration. The conclusions of the meeting were as follows: 4. Data on preparations: No comments 4. Classification and labelling: R50/R53, S60/S61. 5. Recommended restrictions/conditions for use: Revised risk assessment required before

conclusions can be drawn. Areas of concern: Revised risk assessment required before conclusions can be drawn Appendix 1: EPCO discussion table: TRIFLURALIN

Appendix 2: Evaluation table


24/130

Appendix 1: Discussion Table, Trifluralin (Hb) 5. Ecotoxicology No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert

Meeting

5.1/5.2

The risk assessment for birds needs to be discussed. To include birds eating fish.

The RMS had revised the risk assessment in accordance with SANCO 4145 at the request of the Working Group Evaluation and presented this to the meeting. The meeting attempted to discuss this issue, but considered it was too complex and required more detailed consideration. The RMS accepted that a new addendum should be produced.

Still open. RMS to present a revised risk assessment in the form of an Addendum.

5.3 The risk assessment for fish is to be discussed.

Selection of appropriate endpoint was discussed. Novel study, fish (Brown trout) exposed for 24 hours then observed for a year. Growth effects were noted in this study several weeks after the exposure event. Usefulness of this study was questioned. Meeting commented that RMS should propose NOECs for both growth and survival. The meeting questioned the appropriateness of using a TWA approach. If a TWA is used it should be fully justified.

Still open. RMS to present revised risk assessment as an Addendum.

5.4/5.5

The risk assessment for mammals needs to be discussed.

MamTox specialist meeting has not yet taken place. RMS was asked to take note of conclusion from this meeting and the possibility that another NOEC may be appropriate for the risk assessment (e.g. the Hoyt study 1986 148 mg/kg bw day (repro NOEC from multigen. study)

Still open. To be revised after MamTox meeting. Action EFSA/RMS to ensure that MamTox EPCO 4meeting is asked to provide an appropriate repro. NOEC.


25/130


5.6 The risk assessment for earthworms needs to be discussed.

This was done. Fate meeting has now produced new max soil PEC of 3.26 mg/kg. The meeting agreed that the earthworm NOEC for risk assessment should be 14.5 mg/kg soil (adjusted for logpow). Using this NOEC value and the max soil PEC, gives a TER of 4.45. It was agreed that this was acceptable in this case given the worst case assumptions associated with the risk assessment (e.g max soil PEC and NOEC being at the top dose tested).

Fulfilled but RMS to highlight that earthworm NOEC has been modified to take account of the logkow in the endpoint table (e.g NOECcorr) RMS to include revised risk assessment in an Addendum.

Extra info new data in addendum results in new risk assessments as follows: 1. Risk assessment sediment dwellers metabolite TR4 2. Risk assessment soil metabolite TR4 for earthworms 3. Risk assessment microorganisms TR4.

TR4 is an anaerobic soil metabolite this is a MS issue. TR4 is also a major sediment metabolite. The RMS considers the risk from TR4 is acceptable, but the meeting did not consider the new data in detail. Fate meeting identified 2 new metabolites TR14 & TR7. RMS stated that TR14 has similar structure to TR15 for which RA was included in the addendum. TR7 has a similar structure to TR4. RMS to check that PEC has not changed in light of Fate discussion.

Open point: RMS to insert data from TR4 into Endpoint Table. RMS to check risk assessment for TR4 and present as an Addendum. RMS to include risk assessment for TR14 and TR7 in an Addendum.

Clarification of GAP RMS stated that all uses were pre-emergence of the respective crops (cf Fate meeting). For cereals use is post drilling, but pre-em of crop.

RMS to clarify GAP and amend GAP table if necessary.

Revised Evaluation Table

Folowing changes at EPCO2 the RMS tabled an updated Evaluation Table (rev. 0-1 (29.03.04). The meeting agreed that a new Evaluation Table should be produced by the RMS following detailed consideration of all the changes highlight by EPCO2.

Open. RMS to produce revised Evaluation Table.


26/130


Additional point from Fate EPCO2 meeting (Arising from Open Point 4.1)

TR6 and TR15 identified as surface water metabolites from the photolysis study. The RMS is to consider whether photolysis is a major route of degredation and hence whether these metabolites will be environmentally relevant. RMS to include in addendum.

Open point: RMS to consider importance of photolysis and the ecological relevance of metabolites TR6 and TR15 in an Addendum.

Additional point from Fate EPCO2 meeting (Arising from Open Point 4.3)

EPCO2 produced new sed/water DT50 value of 13 days to be used for first tier aquatic risk assessment. RMS is to consider whether this is appropriate to use for this compound.

Open point: RMS to reconsider aquatic risk assessment taking account of the new DT50 and revise Addendum as necessary.

Evaluation table Trifluralin (Hb) EU RESTRICTED 16395/EPCO/BVL/04 rev. 0-2 (03.05.04) Section 5 - Ecotoxicology

27/130

Appendix 2: Evaluation Table 5. Ecotoxicology No.






Open point 5.1: The risk assessment for birds needs to be discussed in an expert meeting.

.

The risk assessment has been revised strictly in accordance with the latest version of SANCO/4145/2000 and sent to the RMS for inclusion in the DAR. At tier 1, TERa values range from >35 to >283, TERst values range from 16 to 72 and TERlt values range from ≥2.8 to ≥13. The only TER value below its Annex VI trigger is the TERlt of 2.8 for insectivores. Based on a realistic exposure, this is refined to ≥5.9

Trifluralin risk assessment for Birds and Mammals according to Sanco/4145/2000. The relevant end points are LD50> 2250 (mg as/kg b.w.) for acute, 573.9 (mg as/kg bw/day) for short term and NOEC=102.85 mg as/kg bw/day for long term toxicity considering that the product is applied once on bare soil. The relevant RUD for acute toxicity a. for soil-dwelling insects is 1 (90%) and for short and long term toxicity is 0,1 (50%) (Aldenberg and Jaworska (2000) according to the Guidance Document on Risk Assessment for Birds and Mammals, Appendix II-9, Table 10 or b. 14 for acute toxicity and 5,1 for short and long term toxicity (large insects). Applications of trifluralin are made pre-emergence to bare soil. Larger, ground-dwelling insects are therefore the likely food

EPCO 3 (28.-29.04.2004): Open point still open. RMS to present a revised risk assessment in the form of an Addendum..


28/130

No.





continued Open point 5.1: The risk assessment for birds needs to be discussed in an expert meeting.

insects are therefore the likely food item for birds. TER 1 risk assessment for leafy crop and cereals: Acute risk assessment The TER values for insectivorous bird are a. >1802 (RUD=1), b. >129 (RUD=14). The TER value for earthworm eating bird is >122 and for fish eating bird is >283. Short-term risk assessment The TER values for insectivorous bird are a. 4591 (RUD=0,1), b. 90 (RUD=5,1). The TER value for earthworm eating bird is 31 and for fish eating bird is 72. All of these TERA and TERST values exceed the Annex VI trigger value of 10. Long-term risk assessment The TER values for insectivorous bird are a. >822 (RUD=0,1), b. >16,1


29/130

No.






(RUD=5,1). The TER values for earthworm eating bird is >5,6 and for fish eating bird is >13. All of these TERLT values exceed the Annex VI trigger value of 5.

Open point 5.2: RMS to revise the risk assessment for fish eating birds in an addendum.

See above. The TER values based on a 1 m “no-spray zone are TERa >283, TERst 72 and TERlt ≥13.

See above. TER 1 risk assessment for leafy crop and cereals on a 1 m “no-spray zone”: Acute risk assessment The TER value for fish eating bird is >283. Short-term risk assessment The TER value for fish eating bird is 72. All of these TERA and TERST values exceed the Annex VI trigger value of 10. Long-term risk assessment The TER values for fish eating bird is >13. This TERLT value exceed the Annex VI trigger value of 5.

EPCO 3 (28.-29.04.2004): Open point still open. RMS to present a revised risk assessment in the form of an Addendum..


30/130

No.





Open point 5.3: RMS to include the revised risk assessment on fish, mentioned in the reporting table (No. vii), in an addendum to be discussed in an expert meeting.

The chronic risk assessment has been conducted assuming (i) continuous exposure to the TWAC and (ii) episodic exposure to a peak concentration plus an extensive development period. The TERlt values are 13 and 11, respectively, providing the 5 m “no-spray” zone is observed. Additional risk assessments for the metabolites of trifluralin have been sent to the RMS for inclusion in the DAR.

According to fate & behaviour data trifluralin readily adsorbs to sediments and dissipation from the water column will be rapid (DT50 ca. 6 hours). Consequently, exposure in the field will be characterised by a brief exposure to relatively high concentrations, followed by rapid dissipation. The rapid dissipation by itself is a strong argument for not conducing long term trials. It is possible to refine the chronic risk to fish according to two different scenarios i.e. (i) a continuous exposure to low concentrations and (ii) a brief exposure to peak concentrations followed by a prolonged developmental period. Continuous exposure to low concentrations Due to the rapid dissipation of trifluralin in water, it is appropriate to refine the chronic risk by comparing the 35 day chronic NOEC of 0.3 µg as/L with the 35-day TWA concentrations based on the DT50 of ca. 6 hours. The refined TERlt values based on chronic exposure are 2,6 and 13 (at 1 and 5 m “no-spray” zones).

EPCO 3 (28.-29.04.2004): Open point still open. RMS to present revised risk assessment as an Addendum.


31/130

No.





continued Open point 5.3: RMS to include the revised risk assessment on fish, mentioned in the reporting table (No. vii), in an addendum to be discussed in an expert meeting.

According to these TERlt values, based on chronic exposure, there would be no unacceptable long-term risks for fish, providing a minimum “no-spray” zone of 5 m. Brief exposure to peak concentrations The chronic risk assessment for fish is refined using the 24-hour NOEC of 25 µg/L (24h exposure plus 1 year development period). The refined TERlt values are 2 and 11 (at 1 and 5 m “no-spray” zones). The Annex VI minimum TERLT of 10 is met with a “no-spray” buffer zone of 5 m.

Open point 5.4: RMS to include endpoints based on daily doses for birds in DAR and list of endpoints.

See Open Point 5.1. All TERst and TERlt values now based on “daily dose”.

The relevant end points are LD50> 2250 (mg as/kg b.w.) for acute, 573.9 (mg as/kg bw/day) for short term and NOEC>102.85 mg as/kg bw/day for long term toxicity. All these values are included in the revision of the list of end-points.

EPCO 3 (28.-29.04.2004): Open point still open. To be revised after MamTox meeting. Action EFSA/RMS to ensure that MamTox EPCO 4 meeting is asked to provide an appropriate repro. NOEC.

Open point 5.5: RMS to include endpoints based on daily doses for mammals in DAR and list of endpoints.

The risk assessment has been revised in accordance with SANCO/4145/2000 and sent to the RMS for inclusion in the DAR. At tier 1, TER values range from TERa

The relevant end points are LD50> 5000 (mg as/kg b.w.) for acute and NOAEL for kidney changes was 200 ppm, equivalent to a dosage of 10.7 mg/kg bw/day, for long term

EPCO 3 (28.-29.04.2004): Open point still open. To be revised after MamTox meeting. Action EFSA/RMS to ensure that


32/130

No.





continued Open point 5.5: RMS to include endpoints based on daily doses for mammals in DAR and list of endpoints.

>87 to >187 and TERlt 2.8 to 2.2. The TERlt values have been refined and exceed the Annex VI trigger for insectivores and fish-eating species. In order to refine the risk to mammals eating earthworms, however, actual residue data are required.

toxicity. The chronic LOAEC was 813 mg/kg, equivalent to a dosage of 30 mg/kg bw/day, based on renal transitional cell carcinoma in two male rats (3.4%) at this dosage. All these values are included in the revision of the list of end-points. Trifluralin risk assessment for Birds and Mammals according to Sanco/4145/2000 always considering that the product is applied once on bare soil. According to the same Guideline there is no exposure for insectivorous mammals for the proposed crops according to the GAP (i.e. “early application” to leafy crops or cereals). TER 1 risk assessment for leafy crop and cereals: Acute risk assessment The TER values for earthworm eating mammal is >39 and for fish eating mammal is >187. All of these TERA values exceed the Annex VI trigger value of 10. Long-term risk assessment The TER values for earthworm eating bird is 0,5 and for fish eating bird is 2,2. All of these TERLT values are below th A VI t i l f 5

MamTox EPCO 4 meeting is asked to provide an appropriate repro. NOEC.


33/130

No.






the Annex VI trigger value of 5. For mammals feeding on fish, exposure may be refined by considering the effect of the 5 m “no-spray” zone proposed to mitigate against adverse effects on aquatic organisms. The revised TERLT value is 11. Another option is to adopt the chronic LOAEC of 813 mg/kg (30 mg/kg bw/day) as the critical endpoint on the grounds that the incidence of renal transitional cell carcinoma was low at this dose (in two male rats only, equivalent to 3.4%) and that these renal tumours arose by a non-genotoxic mode of action and did not occur in female Fischer rats or in two other strains of rat or in mice. Revised TERLT values based on this endpoint are values for earthworm eating bird is 1,3 and for fish eating bird is 6,1. According to this approach, there would be no unacceptable long-term risks for mammals feeding on fish, but the high theoretical residue levels predicted for earthworms would still indicate a cause for concern. An alternative approach would be to


34/130

No.






refine the exposure. As in the avian risk assessment, long-term exposure to residues is most likely to occur from earthworms absorbing residues from soil-incorporated trifluralin (any material remaining on the soil surface would be rapidly photolysed, thereby removing the risk of long-term exposure). The highest risk indicated from the TER values above appears to come from earthworms and this would also be anticipated from the likelihood of uptake from soils, given the more permeable nature of the earthworm cuticle. Consequently, actual residue levels determined in earthworms exposed to trifluralin-treated soil could be used to refine the long-term risk assessment for mammals consuming earthworms. It is recommended, therefore, that the Notifier generates such data.

Open point 5.6: RMS to revise the risk assessment for earthworms in an addendum.

The risk assessment has been revised in accordance with SANCO/10329/2002 and sent to the RMS for inclusion in the DAR. Tier 1 TERa values are >313, 484 and >150 for the active substance, its metabolite TR-4 and its formulated product EF-1521, even

The LC50 values multiplied by the correction factor of 0.5 (to account for the high organic carbon content of the OECD soil), will lead to the lowest possible TERA or TERLT values. TER 1 risk assessment: Acute risk assessment

EPCO 3 (28.-29.04.2004): Open point still open. RMS to highlight that earthworm NOEC has been modified to take account of the logkow in the endpoint table (e.g NOECcorr)


35/130

No.





continued: Open point 5.6: RMS to revise the risk assessment for earthworms in an addendum.

when the correction factor of 0.5 is applied. The tier 1 TERlt of 3.0 is revised to 9.1 when re-calculated according to SANCO/10329/2002.

The TER values for acute toxicity are >313 for trifluralin and >150 for the formulation. All of these TERA values exceed the Annex VI trigger value of 10. Long-term risk assessment The TER value for long term toxicity is > 3 for the formulation. This value is below the Annex VI trigger value of 5. No adverse effects on earthworm survival, growth or reproduction were observed at a treatment rate equivalent to 7,200 g as/ha (9.6 mg as/kg). In the sub-acute study (Ref. MJ15) the test material was applied at the maximum rate of 15 L product/ha (7245 g as/ha). Since the vessels had a surface area of 200 cm2 and contained 500 g dry weight of soil, the actual treatment in the study was equivalent to 28.98 mg as/kg dry soil. This NOEC is then adjusted to 14.49 mg as/kg dry weight by applying the factor of 0.5 (to allow for the high organic carbon content of the soil) and compared to the PECS. The revised TERlt is ≥ 9.1, which confirms that there is no

RMS to include revised risk assessment in an Addendum.


36/130

No.





unacceptable long-term risk to earthworms.

New open point 5.7 Extra info new data in addendum results in new risk assessments as follows: 1. Risk assessment sediment dwellers metabolite TR4 2. Risk assessment soil metabolite TR4 for earthworms 3. Risk assessment microorganisms TR4.

EPCO 3 (28.-29.04.2004): Open point still open: RMS to insert data from TR4 into Endpoint Table. RMS to check risk assessment for TR4 and present as an Addendum.

New open point 5.8 Fate EPCO2 meeting identified 2 new metabolites TR14 & TR7.

Open point still open. RMS to include risk assessment for TR14 and TR7 in an Addendum.

New open point 5.9 Clarification of GAP

EPCO 3 (28.-29.04.2004): Open point still open. RMS to clarify GAP and amend GAP table if necessary.

New open point 5.9 Revised Evaluation Table

EPCO 3 (28.-29.04.2004): Open point still open. RMS to produce revised Evaluation Table.


37/130

No.





New open point 5.10 from Fate EPCO 2 meeting (Arising from Open Point 4.1) TR6 and TR15 identified as surface water metabolites from the photolysis study.

EPCO 3 (28.-29.04.2004): Open point still open. RMS to consider importance of photolysis and the ecological relevance of metabolites TR6 and TR15 in an Addendum.

New open point 5.11 from Fate EPCO 2 meeting (Arising from Open Point 4.3) a new sed/water DT50 value of 13 days.

EPCO 3 (28.-29.04.2004): Open point still open. RMS to reconsider aquatic risk assessment taking the proposed DT50 of 13 days and revise Addendum as necessary.


38/130

List of representative uses evaluated* Trifluralin 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

(d-f)

Conc. 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

Oilseed rape Northern and Southern Zones

EF-1521 F Grass and broad-leaved weeds

EC 480 g/L

BI Pre A/S 1 NA 0.08-0.8 150-600 0.48-1.2 NA

Sunflower Northern and Southern Zones


EC 480 g/L

BI Pre S 1 NA 0.08-0.8 150-600 0.48-1.2 NA

Cotton Southern Zone


EC 480 g/L

BI Pre S 1 NA 0.08-0.48

200-600 0.48-1.2 NA

Winter Cereals Northern and Southern Zones


EC 480 g/L

BS Pre A 1 NA 0.096-0.74

150-600 0.576-1.2

NA

Low rate in light soils, high rate in heavy soils The dose should not exceed the 1.2 kg a.s./ha

BI = Broadcast spray to bare soil followed by incorporation into soil BS = Broadcast spray to bare soil without incorporation Pre = Pre-sowing Post = Post sowing A = Autumn , S= Spring, NA = Not applicable

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

EPCO Expert Meeting 04 (10 – 12 May 2004) 18002/EPCO/PSD/04 Trifluralin 17 May 2004

39/130

REPORT OF EPCO EXPERT MEETING TRIFLURALIN Rapporteur Member State: GREECE Specific comments on the active substance in the section Mammalian toxicology are already listed in the relevant reporting table. Comments submitted for this meeting are listed below. 1. Comments submitted for this meeting: There were no comments submitted for this meeting.


Date Supplier File Name 22 December 2003 RMS/Greece Trifluralin consultation report 22 December 2003 RMS/Greece Trifluralin addendum 1 09 January 2004 RMS/Greece Trifluralin end points 04 February 2004 RMS/Greece Trifluralin reporting table rev1-1 29 March 2004 RMS/Greece Trifluralin evaluation table rev0-1

3. Documents tabled at the meeting: There were no documents tabled at the meeting.

The conclusions of the meeting were as follows: 4. Data on preparations:

A data package for one formulation was considered (EF1521). 5. Classification and labelling:

R43 (R40 to be decided by ECB). 6. Recommended restrictions/conditions for use:

None (to be confirmed following consideration of operator exposure issues).

Areas of concern: 1. Absence of clear NOAEL for tumours in male rat kidney. 2. Acceptable uses to be determined following revision of operator

exposure calculations. Appendix 1: EPCO discussion table: TRIFLURALIN Appendix 2: Evaluation table


40/130

Appendix 1: Discussion Table, Trifluralin (Hb) 4. Mammalian Toxicology No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert

Meeting

(i) Open Point 4.1: RMS to check whether the provision of a 90-day dog study is necessary.

The Meeting noted that additional studies existed but were not available to the current Notifiers. The experts noted that although a 90 day dog study had not been provided, a one year dog study was available and there were no concerns regarding the acceptability of the one year dog study. The Meeting concluded that the one year dog study was adequate for the risk assessment and a 90 day dog study would not be required.

Open Point fulfilled.

(ii) Data Requirement 4.2: Notifier to submit additional 2-year chronic toxicity/carcino-genicity study in rats.

The RMS reported that they did not expect the additional study (not available to the current Notifiers) to result in different conclusions for the risk assessment (the study used a different strain of rats, but there was not normally a requirement to use any particular strain for this type of study). Published details of the additional study had been provided. The Meeting agreed that even if the additional study was not available to the current Notifiers, it was not necessary to require a new study to be performed.

Data requirement fulfilled.

(iii) Open Point 4.3: RMS to check whether the results of the Hoechst study would alter the risk assessment within one week.

The RMS was unable to consider the ‘Hoechst’ study further since it could not be submitted by the Notifiers. However published information on the study had been presented and this did not raise any concerns. The Meeting agreed that if the additional study was not available to the current Notifiers then this study could not be considered further, but no developmental effects appeared to have been identified.



41/130


(iv) Data Requirement 4.4: Notifier to submit study on developmental effects in rats if endpoint of the study is considered essential for further risk calculations.

The Meeting agreed that if this additional rat developmental study was not available to the current Notifiers, it was not necessary to require a new study to be performed. There were no obvious concerns regarding developmental effects based on the published information available (see Open Point 2.2).


(v) Open Point 4.5: RMS to transfer the summary of the two generation reproductive study in column 3 of the reporting table (xix) and the attachment to the reporting table into the revised version of the DAR or to an addendum.

No discussion required on this Open Point. The RMS had presented the requested information in the Addendum.


(vi) Data Requirement 4.6: Task Force should provide information on endocrine disruptive effect.

The Meeting agreed that there was only limited evidence for endocrine effects, with the effects recorded at high dose levels being difficult to distinguish from systemic toxicity. The Meeting concluded that there was no clear evidence for endocrine disrupting effects and the data requirement was considered to have been met.



42/130


(vii) Data Requirement 4.7: Notifier to submit in vitro genotoxicity (Ames-test, chromosome aberration test and gene mutation on mammalian cells test (TK+/-)) and acute oral toxicity tests for the plant metabolites TR-22 and TR-28 or alternatively metabolism study in oilseeds with identification of the metabolites in the seeds.

The Meeting had received a report from the residues expert meeting (EPCO5) that the proposed use on oilseeds giving rise to this requirement was not supported by appropriate crop metabolism data. The toxicological significance of these metabolites did not therefore need to be considered.

Data requirement deleted, it is no longer relevant.

(viii) Open Point 4.8: Setting of ARfD to be discussed at an expert meeting.

The Meeting considered the overall database and examined the results of the rabbit developmental study, but concluded that the effects reported were not of concern for acute toxicity. It was concluded that an ARfD was not required for trifluralin.



43/130


(ix) Open Point 4.9: Notifier to submit data on volatility of trifluralin in the spraying solution and the risk of exposure for the operator from inhalation of the vapour during spraying. Open Point 4.10: Notifier to submit data on volatility of trifluralin in the spraying solution and the risk of exposure for the bystander from inhalation of the vapour during spraying.

The Meeting accepted the case made by the Notifier that the potential for inhalation exposure was low and that no concerns had been identified in the 21 day rat inhalation study. The Meeting concluded that no further consideration of inhalation exposure was required for operators or bystanders.


(x) Open Point 4.11: Request from EPCO3 to set a reproductive NOAEL applicable to ecotox assessment.

The Meeting had received a request from the ecotox expert meeting (EPCO3) for a NOAEL to be set from the multigeneration studies which could be applied to ecotox assessments i.e. relevant to reproductive effects at the population level. The Meeting agreed that the results of the two multigeneration studies could be combined to derive a NOAEL of 148 mg/kg bw/day which would be relevant to population level effects.

Open Point fulfilled. NOAEL of 148 mg/kg bw/day should be used for ecotox assessments.


44/130


(xi) Open Point 4.12: Establishment of an adequate margin between the ADI and the dose level giving rise to tumours in the 2 year rat study.

The Meeting noted that the low dose level in the 2 year rat study was a LOAEL since a low incidence of kidney tumours had been identified in male rats at this dose level, and the explanation provided by the Notifier (referring to alpha-2 globulin accumulation) was not considered to be adequate. The Meeting concluded that the Notifier should provide a more robust explanation for the male rat kidney tumours, possibly including mechanistic data and/or historical control data, and that the ADI should be set at a lower level in the interim. The Meeting agreed that the interim ADI should be set at 0.015 mg/kg bw/d (using a safety factor of 2000) to ensure that an adequate margin existed between the possible LOAEL for tumours and the ADI.

Open point still open. Notifier has the option to provide further information on the relevance to humans of the kidney tumours in male rats, to include mechanistic data and/or historical control data. RMS to revise the endpoints sheet and DAR.

(xii) Open Point 4.13: Assessment of the quality of the dermal penetration data.

The Meeting concluded that due to limitations in the study and on the basis of concerns with the quality of the in vivo dermal penetration study (not all material accounted for, small group size), the default value of 10% should be used (instead of 1%) in operator risk assessments for exposure to the diluted spray solution as well as for exposure to concentrated formulation. The use of ethanol-based formulation in the study compared with xylene-based products was also noted by the Meeting.

Open Point still open. RMS to revise operator risk assessments using dermal penetration values of 10% for both concentrate and dilute spray solution. Revisions to be included in an addendum. RMS to amend endpoint sheet to indicate that an ethanol-based formulation was used in the dermal penetration studies.

Evaluation table Trifluralin (Hb) EU RESTRICTED 18002/EPCO/psd/04 rev. 0-2 (17.05.04) Section 4 – Mammalian Toxicology

45/130

Appendix 2: Evaluation Table

WORKING DOCUMENT – DOES NOT NECESSARILY REPRESENT THE VIEWS OF THE EFSA 4. Mammalian Toxicology No.




Column D Recommendations EPCO-Peer Review Meeting / Conclusions of the evaluation group



Open point 2.1: RMS to check whether the provision of a 90-day dog study is necessary.

The provision of a 90-day dog study is not necessary. A 12-month dog study is summarised in the DAR and judged acceptable by the RMS – no MS has challenged this evaluation. The Task Force are prepared for the 12-month study data to represent the short-term toxicity of trifluralin in the dog. The reports of studies conducted by other companies (i.e., those cited in item no. (ix) of the Reporting Table) are not our property and are not available to the Task Force or the RMS. However, relevant data and findings of many studies are published in the peer-reviewed literature (Ebert, et al., 1992. Fd Chem. Toxic. Vol. 30, No. 12 pp. 1031-1044).

An oral 90 day dog study was not conducted, but an 1 year oral toxicity study in dogs was submitted by the notifier and evaluated by the RMS. The 1 year dog study was judged acceptable by the RMS and is considered to represent the short-term toxicity of trifluralin in the dog. Thus, the submission of an 90 day dog oral toxicity study is not considered to be necessary.

EPCO 6 (10 – 12 May 2004): Open point fulfilled.


46/130

No.





2.1

Notifier to submit additional 2-year chronic toxicity/carcinogenicity study in rats.

ti d

The Task Force submitted information on four carcinogenicity studies in the rat, one of which was classed as acceptable in the DAR (Vol. 3, B.6.5.1/01). The only significant deviation from EC test guideline B.33 was the absence of a NOEL based on the presence of tumours in 3 male rats at 800 ppm - 30 mg/kg/d (1/59 males had urinary bladder papilloma and 2/59 had renal carcinoma). The tumours were associated with renal calculi and for several reasons (explained in a detailed paper cited in the Reporting Table, item xii) they are considered not relevant to humans. Independent of this position, it is a fact that tumours cannot occur at a dose that does not cause either renal calculi or renal toxicity. Mechanistic studies show a NOEL for any renal effect of 50 ppm or 2.6 mg/kg/d. This dose, which is more than 10-times lower than the dose that caused tumours in 5% of male rats, is the proposed ‘chronic rat NOEL’. The ‘Hoechst study’ cited in the Reporting table (Donaubauer & Schütz, 1986) in rats shows no carcinogenic potential at levels up

The RMS agrees with the notifier`s comment. According to the DE comment cited in the Reporting Table, the Hoechst study involves chronic toxicity of trifluralin in Wistar rats. Thus this study is not expected to retract or support the conclusions derived from the Fischer rat chronic toxicity study, neither is it expected to provide clarification on the issues raised in the Ficher rat chronic toxicity study.

EPCO 6 (10 – 12 May 2004): Data requirement fulfilled.


47/130

No.





2.1

continued Notifier to submit additional 2-year chronic toxicity/carcinogenicity study in rats

to 3200 ppm after 122 weeks of treatment and supports an ADI double that proposed in this evaluation. The relevant data and findings of this 2-year chronic toxicity/carcinogenicity study in rats are published in the peer-reviewed literature (Ebert, et al., 1992. Fd Chem. Toxic. Vol. 30, No. 12 pp. 1031-1044). This paper will be submitted by the Task Force, as requested. The Task Force considers that this data requirement has been fulfilled.

Open point 2.2: RMS to check whether the results of the Hoechst study would alter the risk assessment within one week.

As mentioned in the preceding item, the ‘Hoechst study’ shows no carcinogenic potential at levels up to 3200 ppm after 122 weeks of treatment and supports an ADI double that proposed in this evaluation (Ebert, et al., 1992. Fd Chem. Toxic. Vol. 30, No. 12 pp. 1031-1044). In conclusion, the results of the ‘Hoechst study’ would not alter the risk assessment to consumers. This conclusion also applies to the ‘Hoechst study’ on developmental effects in rats referred to in item no.

The RMS has not evaluated the ‘Hoechst study’ and therefore any conclusions on whether the results of this study would alter the risk assessment are based on the data presented in the Reporting Table. According to these data the NOAEL of the developmental toxicity study in rats (Baeder et al., 1983) was set at 20 mg/kg b.w./day based on growth retardation and prenatal losses at 100 mg/kg b.w./day. The RMS considers that the ‘Hoechst study’ is not expected to alter the risk assessment of t ifl li f th f ll i



48/130

No.





2.2, below.

trifluralin for the following reasons: - The NOAEL for the ‘Hoechst study’ is based on toxicological end-points (growth retardation, prenatal losses) similar to the ones observed in the other accepted developmental toxicity studies presented in the DAR.

- The RMS considers that the overall lowest relevant developmental NOAEL would most probably not change even if this study was also taken into account due to the range of the doses selected (i.e. the dose of 50 mg/kg b.w./day was not assessed in the ‘Hoechst study’).

- The NOAEL of 20 mg/kg b.w./day, even if it is considered as the lowest relevant developmental NOAEL value it is approximately 10-fold higher than the NOAEL’s used for the derivation of the ADI and AOEL values.

2.2 Notifier to submit study on developmental effects in rats if endpoint of the study i id d ti l f

With regard to the ‘Hoechst’ rat teratology study cited in the Reporting table (Baeder et al., 1983) thi i t th t f th

The RMS considers that the ‘Hoechst study’ is not expected to alter the risk assessment of t ifl li l i d i d t il i

EPCO 6 (10 – 12 May 2004): Data requirement fulfilled.


49/130

No.





is considered essential for further risk calculations.

1983), this is not the property of the Task Force and cannot be submitted. The DAR already contains three such studies, all of which were deemed acceptable. As mentioned in the Reporting table, the NOAEL for the ‘Hoechst’ rat teratology study was 20 mg/kg/d. The ADI and AOEL for trifluralin are based on much lower NOAEL’s (2.4 & 2.6 mg/kg/d) such that even if a 4th study were available it would not alter any risk assessments for humans.

trifluralin, as explained in detail in preceding Open Point 2.2.

Open point 2.3: RMS to transfer the summary on the two generation reproductive study in column 3 of the reporting table (xix) and the attachment to the reporting table into the revised version of the DAR or to an addendum.

No comment The RMS noted that by mistake the attachment to the reporting table was entitled: “Reporting Table Section 2, point No. (xix)”, when it refers to point (xx). The Addendum was prepared on point (xx) of the reporting table and it includes the comments on column 3 and the attachment.



50/130

No.





2.3

Task Force should provide information on endocrine disruptive effect.

This requirement was raised by comments from the UK, based primarily on effects in three rabbit teratology studies but also reproduction studies (Evaluation table points xxiv-xxvii, DAR Vol.3 point B.6.6.2.2./01-03). Most of the points raised by the UK are not accompanied by any reasoning. Fortunately, most of the points are more than adequately addressed by the RMS in the Reporting table and have been agreed by MS – the RMS should be commended. For example: - In one 2-gen. study (xix; Vol. 3 B.6.6.1.1/01) the incidence of ‘runts’ was neither dose-related nor statistically significant; - In another 2-gen. study (xx; Vol. 3 B.6.6.1.1/02) uterine atrophy occurred only at a very high dose that caused excessive maternal toxicity and was 3.4 million times higher than a human Total TMDI; - In a rabbit teratology study (xxiv; Vol. 3, B.6.6.2.2./01) resorptions were increased and placental weights were reduced. However, the ‘increase’ in resorptions was

l 2 3%! Pl t l i ht

No comment EPCO 6 (10 – 12 May 2004): Data requirement fulfilled.


51/130

No.





2.3

continued Task Force should provide information on endocrine disruptive effect.

only 2.3%! Placental weights were reduced but so were foetal weights at a dose that caused up to 40% reduced maternal food intake and body weight loss during organogenesis; - In a rabbit teratology study (xxv; Vol. 3 B.6.6.2.2./02) an increase in ‘runts’ and sex ratio occurred only at a dose that exceeded a maternal MTD (e.g., 20% died, 30% aborted);- In a rabbit teratology study (xxvi; Vol. 3, B.6.6.2.2./03) an increase in ‘runts’ and sex ratio occurred only at maternally toxic doses (e.g., 40% reduced maternal food intake and body weight loss during organogenesis at the mid-dose!). In summary, there are effects at high, maternally toxic doses - many of which clearly exceeded an MTD - but no evidence of selective endocrine disruption.

2.4

Notifier to submit in vitro genotoxicity (Ames-test, chromosome aberration test and gene mutation on mamalian cells test (TK+/-)) and acute oral toxicity tests for the plant metabolites TR 22 d TR 28

With due respect, the Task Force believes there must be a serious misunderstanding for a MS to contend that testing of metabolites (including animal studies) is justified in this specific case. Plant metabolites TR-22 and TR-28

In correlation with the point 3.1 of the Evaluation table (Residues), RMS agrees with the notifier’ s position. More specific, the metabolites TR-22 and TR-28 were not detected in rat metabolism studies but were found in the non edible part of plants i e in the roots

EPCO 6 (10 – 12 May 2004): As the proposed use on oilseed giving rise to this data requirement was not supported by appropriate metabolism data, the toxicological significance of these metabolites was considered not to be necessary.


52/130

No.





TR-22 and TR-28 or alternatively metabolism study in oilseeds with identification of the metabolites in the seeds.

were identified in a non-edible portion (roots) of mustard plants, where they represented <1% and 1.2% of the total residue, respectively (i.e., < 0.01 mg/kg – in compliance with 91/414/EEC, there was no need for these metabolites to be identified…). TR-22 and TR-28 levels were more than 20-times lower than trifluralin. Trifluralin residues in edible portions of all crops were always <LOQ of 0.01 mg/kg. Based on these data, the level of each metabolite in edible portions would be < 0.0005 mg/kg (i.e., 0.01 mg/kg ÷ 20) and the Total TMDI would be 0.000005 mg/kg bw/day*. For this to be a health concern the ADI for the metabolite would have to be less than the Total TMDI or < 0.000005 mg/kg bw. This is lower than the ADI for any known pesticide, in fact it is lower than the ADI for any known substance as cited in the ‘Relevant Metabolites’ document. In other words, a metabolite would have to be almost 5000-times more toxic than trifluralin to even begin to be a concern, at tier 1 level.

edible part of plants, i.e. in the roots of mustard plants in amounts <1% and 1.2% of the total residue respectively, that corresponds to < 0.01 mg/kg concentration that is triggered for identification of any metabolites. In addition, the rationale stated by the notifier for the very low TMDI estimated for these metabolites, when compared with the parent compound trifluralin is very much acceptable. Therefore, besides that no information concerning their toxicity was available, the question whether these two metabolites are of toxicological concern or not, is not of relevance anymore.

Data requirement deleted.


53/130

No.





2.4

continued Notifier to submit in vitro genotoxicity (Ames-test, chromosome aberration test and gene mutation on mamalian cells test (TK+/-)) and acute oral toxicity tests for the plant metabolites TR-22 and TR-28 or alternatively metabolism study in oilseeds with identification of the metabolites in the seeds.

However, regarding their toxicity, there is reason to believe they are likely to be less toxic, not 5000-times more toxic, than the parent because: - TR-22 is trifluralin minus all fluorine atoms and one propyl group (i.e., it is the same as rat metabolite A (‘A’) after ‘A’ has been detoxified by replacement of the trifluoromethyl group with a more polar acid function); - TR-28 is simply a dimer of a known rat metabolite, ‘A’ . Unless our rationale is seriously flawed, common sense must prevail, and unnecessary testing must be avoided. * (The DAR’s most conservative Total TMDI of trifluralin for the most vulnerable subpopulation assuming concurrent exposure to all crops potentially treated with trifluralin all at the MRL based on the LOQ, is 0.0001 mg/kg bw/day, ÷ 20 = 0.000005 mg/kg bw/day).


54/130

No.





Open point 2.4: Again, the RMS is to be commended for such clear and categorical responses to other MS. The Task Force believes that there are no selective toxicological alerts that could conceivably be elicited by a single dose and an ARfD is not justified. However, as residues in all crops are so low (all <LOQ of 0.01 mg/kg) and trifluralin products are not directly applied to crops of primary concern for acute exposure (e.g., potentially ‘hot’ single items such as carrots, apples, potatoes), setting an ARfD would be an academic exercise.

No comment EPCO 6 (10 – 12 May 2004):

2.5 Notifier to submit data on volatility of trifluralin in the spraying solution and the risk of exposure for the operator from inhalation of the vapour during spraying.

The Task Force do not have data on the volatility of trifluralin from a spray solution but this is not important. Henry’s Law Constant cited in the Reporting table is relevant for loss from a water body, not a spray. However, trifluralin is applied by boom sprayer onto bare soil and typically is immediately incorporated into the soil. Under these conditions loss by evaporation is minimal (e.g., < 1% of applied dose over a 6-hour period – DAR, Vol. 3, B.8.7) and is not a cause for concern for an operator or a bystander.

The RMS accepts the justification provided by the notifier taking into account the results of the 21 day inhalation toxicity study in rats (DAR, Vol. 3, B.6.3.3.1/01).

EPCO 6 (10 – 12 May 2004): The Meeting accepted the case made by the Notifier that the potential for inhalation exposure was low and that no concerns had been identified in the 21 day rat inhalation study. It was concluded that no further consideration of inhalation exposure was required for operators or bystanders Data requirement fulfilled.


55/130

No.





It is also relevant to note that 2-week exposure to a saturated atmosphere of trifluralin vapours produced no effects, even on the most sensitive markers of toxicity, in rats (Vol. 3, B.6.3.3.1/01).

2.6 Notifier to submit data on volatility of trifluralin in the spraying solution and the risk of exposure for the bystander from inhalation of the vapour during spraying.

Refer to preceding point, 2.5. EPCO 6 (10 – 12 May 2004): The Meeting accepted the case made by the Notifier that the potential for inhalation exposure was low and that no concerns had been identified in the 21 day rat inhalation study. It was concluded that no further consideration of inhalation exposure was required for operators or bystanders Data requirement fulfilled.

Message from EPCO 3 EPCO 4 to set a reproductive NOAEL applicable to ecotox assessment

The NOAEL of 148 mg/kg bw/day should be used for the ecotoxicological risk assessment.


56/130

WORKING DOCUMENT – DOES NOT NECESSARILY REPRESENT THE VIEWS OF THE COMMISSION SERVICES

List of representative uses evaluated*

Trifluralin 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


PHI (days)

(l)

Remarks:

(m) Type

(d-f)

Conc. 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



EC 480 g/L

BI Pre A/S 1 NA 0.08-0.8 150-600 0.48-1.2 NA



EC 480 g/L

BI Pre S 1 NA 0.08-0.8 150-600 0.48-1.2 NA



EC 480 g/L

BI Pre S 1 NA 0.08-0.48

200-600 0.48-1.2 NA



EC 480 g/L

BS Pre A 1 NA 0.096-0.74

150-600 0.576-1.2

NA



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


57/130

(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

EPCO Expert Meeting 05 (11 – 12 May 2004) 18003/EPCO/PSD/04 trifluralin 13 May 2004

58/130

REPORT OF EPCO EXPERT MEETING 05 TRIFLURALIN Rapporteur Member State: GREECE Specific comments on the active substance in the section Residues and Analytical Methods are already listed in the relevant reporting table. Comments submitted for this meeting are listed below. 1. Comments submitted for this meeting:

None.


Date Supplier File Name 22 December 2003 RMS/Greece Trifluralin consultation report 09 January 2004 RMS/Greece Trifluralin end points 04 February 2004 RMS/Greece Trifluralin reporting table rev1-1 29 March 2004 RMS/Greece Trifluralin evaluation table rev0-1 March 2004 RMS/Greece Addendum to Volume 1 March 2004 RMS/Greece Addendum (2) to Volume 3

2. Documents tabled at the meeting:

None. The conclusions of the meeting were as follows: 5. Data on preparations: Not considered at EPCO 5. 4. Classification and labelling: Not considered at EPCO 5. 5. Recommended restrictions/conditions for use: Only uses on cereals in Northern

Europe are supported at present. RMS to seek additional information from notifier on USA trials data in order to further consider uses on cereals in Southern Europe. Uses on oilseeds is not currently supported.

Areas of concern: None Appendix 1: EPCO discussion table: TRIFLURALIN

Appendix 2: Evaluation table


59/130

Appendix 1: Discussion Table, Trifluralin (Hb) 5. Residues (and section 1, points on residue methods of analyses) No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert

Meeting

(i) 1.4 If it is decided that the metabolite TR-4 is included in the residue definition for soil, fully validated analytical methods determining this metabolite in soil will be required.

EPCO 2 (fate and behaviour meeting) proposed that TR4, which is formed in significant quantities only under anaerobic conditions, should be addressed at MS level. It was noted that there may be other significant metabolites which require further consideration as an open point arising from the EPCO 3 (ecotoxicology meeting). [Post-meeting note: EPCO 3 discussed sediment and soil metabolites TR4 (and also TR14 and TR7 as new metabolites identified in EPCO 2). EPCO 3 has proposed an Open point : RMS to insert data from TR4 into Endpoint Table. RMS to check risk assessment for TR4 and present as an Addendum. RMS to include risk assessment for TR14 and TR7 in an Addendum.] Therefore a decision on further methods of analysis for sediment or soil metabolites will be made when the residue definition has been established.

Point is open. Methods of analysis are available only for trifluralin. Subject to ecotoxicology confirmation on whether other metabolites need to be considered in the residue definition for soil/sediment, further methods of analysis determining these metabolites in soil will be required.

(ii) 1.5 If it is decided that the metabolites TR-6 and TR-15 are included in the residue definition for water, fully validated analytical methods determining these metabolites in water will be required.

Outcome dependent on the views of Ecotoxicology as EPCO 3 has an open point regarding the importance of photolysis and ecological relevance of metabolites TR-6 and TR-15. Concern was expressed that metabolites may appear in groundwater , and that we currently do not have methodology to address components that may be expected to be present above 0.1 µg/l. However, in the absence of acceptable marker compound(s), methods of analysis are not usually requested, unless metabolites are considered to be of either fate and behaviour and ecological relevance.

Point is open. If it is decided that the metabolites TR-6 and TR-15 are included in the residue definition for water, fully validated analytical methods determining these metabolites in water will be required.


60/130


(iii) Message from EPCO 4 to EPCO 5: Please consider the need for the toxicology meeting to address the toxicological relevance of metabolites found in roots of mustard plants. Are the plant metabolism data suitable for establishing a residue definition for oilseeds?

See following point.

(iv) 3.1 In case the plant metabolites TR-22 and TR-28 are considered toxicologically relevant a new metabolism study in oilseeds will be necessary.

These metabolites were found at very low concentrations in mustard roots; therefore the notifier and RMS proposes that they are not included in residue definition as the levels were considered too low to be of concern. The meeting noted that these metabolites were not found in the mammalian metabolism. The characterisation of metabolites in oilseeds is limited to leaves and roots of mustard plants, although in the other oilseed metabolism studies significant levels of total radioactivity were analysed in the seeds, and this was not further characterised (maximum level in oilseed seeds was 0.134 mg/kg). Trifluralin was noted as having a high log Pow. Concern was raised that hydrophobic property of components may increase the propensity for association with the seed part of the crop, although systemic transfer of trifluralin is not necessarily expected. The residues trials showed LOQ residue situation for trifluralin at harvest in oilseed crops. If metabolites were similar in having a hydrophobic nature, then these may be accumulating in seeds. The DAR indicates that the total radioactivity in the seeds was increasing with time. The oilseeds metabolism studies were therefore regarded as inadequate to conclude on a residue definition for oilseed, and a new oilseed metabolism study was agreed as necessary to support oilseed uses. These data are needed before the toxicological relevance of metabolites can be

d All il bl l t t b li t di t t GLP d h d

Point is open. A further metabolism study is required for oilseeds, and oilseed uses are not currently supported by available metabolism data. Present studies do not fully address consumer exposure via seeds. For cereals residue definition for Annex 1 listing can be agreed as trifluralin only. End points to be amended to indicate that no clear residue definition has been established for oilseeds. Advice to EPCO 4


61/130


continued 3.1 In case the plant metabolites TR-22 and TR-28 are considered toxicologically relevant a new metabolism study in oilseeds will be necessary.

assessed. All available plant metabolism studies were not to GLP, and many had a fairly recent report date. The RMS clarified that the conduct of the studies pre-dated the requirement for GLP (before 1993) and the reports were a more recent re-presentation of these studies. Sufficient data on metabolite characterisation were available for maize, and the residue definition established for cereals as parent trifluralin only was regarded as acceptable.

(Toxicology): metabolites in oilseeds do not need to be considered at this stage.


62/130


(v) Open Point 3.1

The appropriate number of residue trials for setting MRLs in barley and wheat should be discussed in an expert meeting.

All 6 trials in wheat (4) & barley (2) were conducted in Northern Europe indicating residues of trifluralin were below the LOQ. The available data were regarded as acceptable to support an MRL of 0.05 mg/kg [proposed as 0.05 mg/kg rather than the LOQ of 0.01 mg/kg for practical monitoring purposes].A large number of USA trials were submitted, many were generated in the1960s and 1970s, some at 2-3x GAP rate (wheat). For these exaggerated rate trials residues were also below the LOQ. It was therefore suggested that Southern Europe trials are not required. The maize metabolism study also shows low residue in grain and the residues trials data were seen as consistent with metabolism data. It was decided that a comparability assessment of the USA trials (climate and PHI [PHI was noted as being very long in some of the USA trials]) needed to be made to consider the relevance of the trials to the Southern EU GAP, and the acceptability of the USA trials data needs to be evaluated (e.g. were the methods of analyses for these old trials adequately reported). It was considered that further evaluation is required, although extrapolation from the USA to Southern EU GAP for this case may be possible.

For Southern European uses this point remains open: Regarding confirmation of proposed LOQ residues for SE uses: Notifier to provide further information on conduct and comparability (climate and PHIs) of USA trials to support Southern Europe uses, and RMS to evaluate the acceptability of the USA trials. For Northern European uses the Point is fulfilled: Meeting concluded that sufficient data was available to support an MRL of 0.05 mg/kg for cereals for Northern European uses.

(vi) Open Point 3.2

RMS include calculate the animal intake for oilseed rape forage in an addendum.

The addendum describes 2 trials on oilseed rape showing residues in forage at up to 0.2 mg/kg. Residues of trifluralin were <0.01 mg/kg at harvest. The addendum presented animal intake calculations for forage to take account of an earlier residue in oilseed forage of 0.2 mg/kg. It was noted that the value of 0.2 mg/kg was likely to be a lower residue as this was for a trial where 0.2 mg/kg was the LOQ for that particular trial and other trials were available to suggest residues of <0.01 mg/kg. Based on the residue level of 0.2 mg/kg in forage and animal metabolism studies, consumption of treated rape forage by beef cattle and pigs (poultry and dairy cattle are not fed rape forage) was not expected to trigger need for feeding studies i.e. with reference to products of animal origin. This assumes that residue definition is parent (see point 3.1).

Point is still open. Subject to residue definition being agreed as parent only for oilseeds, meeting concluded that residues in animal products would not be expected. It is not necessary to propose MRLs or residue definitions for animal products.


63/130


(vii) Open Point 3.3

RMS to include a calculation of the potential risk in an addendum in case an ARfD is set.

EPCO 4 have advised that no ARfD is necessary. Point fulfilled. No ARfD is set.

Message from EPCO 4: The revised ADI is 0.015 mg/kg bw/day [notifier has the option to supply further information on the ADI to refine the ADI at a later date.]

The highest intake is for infants (UK model) at 0.000113 mg/kg bw/day. This still equates to <1% of the revised ADI, so the conclusion for risk assessment remains unchanged.

Point fulfilled: conclusion for consumer risk assessment remains unchanged

(viii) End-points (Residues and residue methods)

Point is open End Points to be revised in accordance with the agreements of the meeting.

Evaluation table Trifluralin (Hb) EU RESTRICTED 18003/EPCO/PSD/04 rev. 0-2 (13.05.04) Section 1 – Residue methods of analysis

rapporteur GR 64/130

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




Column D Recommendations EPCO Expert Meeting/ Conclusions of the evaluation group

Data requirements: 5 Open points: 7


Open point 1.1: RMS to include the evaluation of the new study on melting point in an addendum.

No comment The melting point of pure trifluralin is 47.2±0.1 oC (see Addendum to the DAR). No further data are required.

Shifted to EPCO 6 (Section 1)

Open point 1.2: RMS to include the evaluation of the new study on boiling/ decomposition point in an addendum.

No comment The boiling point of pure trifluralin is not determinable due to decomposition. The decomposition temperature is 202±1 oC (see Addendum to the DAR). No further data are required.


1.1 Notifier to submit 2-year storage stability test of formulation EF-1521

This report will be available for submission by the end of April 2004.

The RMS took notice that the 2-year storage stability study will be completed and available for submission by the end of April 2004.




No.





Open point 1.3: RMS to include the evaluation of the new shelf life study in an addendum.

No comment The purpose of the study submitted (Vorhies S., 2003) was to demostrate that the content of impurity N-nitroso-di-n-propylamine (NDPA) in the p.p.p. does not exceed the FAO specified limits throughout the shelf-life period. The data showed that the NDPA content remains at least 50% below the FAO specification limit, even after 2 years of storage (see Addendum to the DAR). The notifier should justify why the study was not conducted under GLP.

Shifted to EPCO 6

1.2 The procedures for cleaning equipment have to be addressed on MS level.

Advice for cleaning equipment is usually contained either on the product label or in leaflets. If this is not the case, procedures which have been supplied to the RMS and will be included in an addendum (see Open Point 1.4 should be followed. Alternatively, techniques which follow good agricultural codes of conduct may be employed.

Information on procedures for cleaning application equipment has been included in the addendum of the DAR.

Shifted to EPCO 6

Open point 1.4: RMS to include information on the effectiveness of cleaning procedures in an addendum.

No comment Information on the effectiveness of cleaning procedures has been included in the addendum of the DAR.

Shifted to EPCO 6



No.





Open point 1.5: RMS to include the information on transport (Road & Rail, Sea and Air) in an addendum.

No comment Information on transport (Road & Rail, Sea and Air) has been included in the addendum of the DAR.

Shifted to EPCO 6



No.





1.3 Notifier to submit LOQ values for the method of analysis for impurities of trifluralin technical.

We agree that the reported ”limit of determination” (0.05%) and calculation of LOQ provided in response to initial DAR comments do not satisfy the definition of LOQ as defined in the SANCO guidance document. For the study in question, precision and accuracy was tested for each impurity (DAR Tables B.5.1.2.1 and B.5.1.2.2). Precision was tested at or near the range of the recovery concentrations (0.10 and 1.00 % w/w), which permit the precision and recovery data to be evaluated jointly. The LOQ may be set as the greater of the concentrations tested for those requirements. For example, precision of impurity 1 was tested at 1.24 % w/w and acceptable recovery was found at 1.0 % w/w; therefore, the LOQ for impurity 1 is 1.24 % w/w. Likewise, LOQ for impurities 2-6 are 0.10, 0.10, 0.15, 0.33, and 0.10, respectively. Each LOQ value is less than the maximum content for the respective impurity.

RMS is satisfied with notifier’s comment. LOQ values for the method of analysis for impurities of trifluralin technical are confirmed and are considered adequately low with regard to the specified maximum content of each impurity. No further data are required.

Shifted to EPCO 6



No.





Open point 1.6: RMS to include evaluation of new analytical method for the determination of the a.s. in the lead formulation in an addendum.

No comment The evaluation of the new analytical method for the determination of the a.s. in the lead formulation EF-1521 has been included in the Addendum of the DAR. The method is acceptable, adequately validated.

Shifted to EPCO 6

Open point 1.7: RMS to include evaluation of the new analytical method for the determination of the Di-n-propyl-nitrosoamine in the lead formulation in an addendum.

No comment The evaluation of the new analytical method for the determination of the relevant impurity di-n-propyl-nitrosoamine in the lead formulation EF-1521 has been included in the Addendum of the DAR. The method is acceptable, adequately validated.

Shifted to EPCO 6

1.4 If it is decided that the metabolite TR-4 is included in the residue definition for soil, fully validated analytical methods determining this metabolite in soil will be required.

We believe that the additional ecotoxicity studies for TR-4 that have been submitted have demonstrated that this metabolite is not relevant and so it should not be included in the residue definition for soil. Therefore, a validated analytical method for the determination of TR-4 in soil should not be required. However, if the RMS does not agree with this conclusion, a method will be developed and validated but until this requirement is confirmed a date for its availability cannot be provided.

RMS accepts the notifier’s comment. No analytical method for the determination of the metabolite TR-4 in soil is required, since it is not included in the residue definition for soil.

EPCO 5 (11-05-2004): Methods of analysis are available only for trifluralin. Subject to ecotoxicology confirmation on whether other metabolites need to be considered in the residue definition for soil/sediment, further methods of analysis determining these metabolites in soil will be required. Data requirement still open.



No.





1.5 If it is decided that the metabolites TR-6 and TR-15 are included in the residue definition for water, fully validated analytical methods determining these metabolites in water will be required.

We believe that the additional ecotoxicity studies for TR-6 and TR-15 that have been submitted have demonstrated that this metabolite is not relevant and so it should not be included in the residue definition for water. Therefore, validated analytical methods for the determination of TR-6 and TR-15 in water should not be required. However, if the RMS does not agree with this conclusion, methods will be developed and validated but until this requirement is confirmed a date for their availability cannot be provided.

RMS accepts the notifier’s comment. No analytical methods for the determination of the metabolites TR-6 and TR-15 in water are required, since they are not included in the residue definition for water.

EPCO 5 (11-05-2004): EPCO 3 has an open point regarding the importance of photolysis and ecological relevance of metabolites TR-6 and TR-15. If it is decided that the metabolites TR-6 and TR-15 are included in the residue definition for water, fully validated analytical methods determining these metabolites in water will be required. Data requirement still open.

Evaluation table Trifluralin (Hb) EU RESTRICTED 18003/EPCO/PSD/04 rev. 0-2 (13.05.04) Section 3 – Residues


3. Residues No.







Message from EPCO 4 to EPCO 5: Please consider the need for the toxicology meeting to address the toxicological relevance of metabolites found in roots of mustard plants. Are the plant metabolism data suitable for establishing a residue definition for oilseeds?

EPCO 5 (11-05-2004): see following point

3.1 In case the plant metabolites TR-22 and TR-28 are considered toxicologically relevant a new metabolism study in oilseeds will be necessary.

We do not believe that these metabolites are toxicologically relevant. However, if it is decided that they are relevant a new metabolism study will be conducted.

We fully agree with the notifiers position (Point 2.4 in Toxicology Section) that these two metabolites were found in the non edible part of plants i.e. in the roots of mustard plants in amounts <1% and 1.2% of the total residue respectively, that corresponds to <0.01 mg/kg concentration that is triggerd for identification of any metabolites. In addition, the rationale stated by the notifier for the very low TMDI

EPCO 5 (11-05-2004): A further metabolism study is required for oilseeds, and oilseed uses are not currently supported by available metabolism data. Present studies do not fully address consumer exposure via seeds. For cereals residue definition for Annex 1 listing can be agreed as trifluralin only. Advice to EPCO 4 (Toxicology): metabolites in oilseeds do not need to



No.





estimated for these metabolites, when compared with the parent compound trifluralin is very much acceptable. Therefore, besides that no information concerning their toxicity was available, the question whether these two metabolites are of toxicological concern or not, can be disregarded.

be considered at this stage. Data requirement still open.

Open point 3.1: The appropriate number of residue trials for setting MRLs in barley and wheat should be discussed in an expert meeting.

The representative uses are for pre-emergence use only – no post emergence uses are supported. The metabolism studies and all of the data generated clearly demonstrate that residue levels are below the LOQ of 0.01 mg/kg. Although the numbers of trials in the EU are less than the norm, the weight of evidence is so overwhelming that additional trials are unlikely to generate a divergent data.

The data package prepared for wheat (4 trials) is sufficient for the support of the use of trifluralin in Northern Europe, since only 2 trials are required in the case of a non residue situation. And here it is clearly a non residue situation. The question is whether the data from US can be used additionally to the 4 European trials to support the extrapolation of residue trials conducted in Northern Europe to South Europe and to our opinion this is possible. The data package prepared for barley (2 trials) is sufficient for the support of the use of trifluralin in Northern Europe, since only 2 trials are required in the case of a non residue situation. And here it is clearly a non residue situation. The

EPCO 5 (11-05-2004): Meeting concluded that sufficient data was available to support an MRL of 0.05 mg/kg for cereals for Northern European uses. For Northern European uses the point is fulfilled. Regarding confirmation of proposed LOQ residues for Southern European uses a data requirement was identified. Data requirement: Notifier to provide further information on conduct and comparability (climate and PHIs) of USA trials to support Southern Europe uses.



No.





question is whether the data from US can be used additionally to support the extrapolation of residue trials conducted in Northern Europe to South Europe and to our opinion this is possible.

Open point 3.2: RMS include calculate the animal intake for oilseed rape forage in an addendum.

No comment Since it is proposed that failure of crop growth of oilseed rape might result in feeding of the remaining product probably containing high levels of trifluralin residues to livestock, we performed the potential intake calculations from oilseed rape forage (potential feeding stuff for beef cattle and pigs), to cover also this case of crop failure. The calculated animal intake is presented in Addendum 2 and it was concluded that although failure of crop growth of oilseed rape may lead to detectable residues above the trigger value in feeding stuffs, this does not lead to detectable residues in edible animal products in the metabolism study conducted with an appropriate dosing level and duration to achieve a plateau in milk. Thus, setting of MRLs for products of animal origin is not

EPCO 5 (11-05-2004): The addendum presented animal intake calculations for treated rape forage assuming that residue definition is parent. Subject to residue definition being agreed as parent only for oilseeds, meeting concluded that residues in animal products would not be expected. It is not necessary to propose MRLs or residue definitions for animal products. Open point fulfilled. Since a new metabolism study in oilseeds is required, a final conclusion on the residue definition for oilseeds and therefore on the livestock dietary burden could not be drawn at this stage. A recalculation of the animal intake for oilseeds might be necessary



No.





appropriate and ruminant or poultry feeding studies are not required. A re-entry period for animal grazing in oilseeds and a withholding period for use of oilseed forage as animal feeding stuff, both of 35 days is proposed .

upon receipt of the new metabolism study.

Open point 3.3: RMS to include a calculation of the potential risk in an addendum in case an ARfD is set.

No comment No comment EPCO 5 (11-05-2004): No ARfD is set. Open point fulfilled.

Message from EPCO 4: The revised ADI is 0.015 mg/kg bw/day [notifier has the option to supply further information on the ADI to refine the ADI at a later date.]

EPCO 5 (11-05-2004): conclusion for consumer risk assessment remains unchanged Message addressed



No.





New open point suggested at EPCO 5 End points to be revised by RMS in accordance with the agreements of the meeting

EPCO 5 (11-05-2004): Need for further action was identified. End points to be amended to indicate that no clear residue definition established for oilseeds. ADI and TMDI figures to be updated. New open point:still open

EPCO Expert Meeting 06 (15-16 June 2004) 16696/EPCO/BVL/04 trifluralin 15 June 2004

75/130

REPORT OF EPCO EXPERT MEETING 06 TRIFLURALIN Rapporteur Member States: Greece 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:

None.


Date Supplier File Name 22 December 2003 RMS/Greece Trifluralin consultation report 09 January 2004 RMS/Greece Trifluralin end points 04 February 2004 RMS/Greece Trifluralin reporting table rev1-1 March 2004 RMS/Greece Trifluralin addendum 2 29 March 2004 RMS/Greece Trifluralin evaluation table rev0-1

3. Documents tabled at the meeting

None. The conclusions of the meeting were as follows: 4. Data on preparations: EF1521. 5. Classification and labelling: not discussed 6. Recommended restrictions/conditions for use: not discussed Areas of concern: none Appendix 1: EPCO discussion table: TRIFLURALIN Appendix 2: Evaluation table


76/130

Appendix 1: Discussion Table, Trifluralin (Hb) 1. Physical and Chemical Properties No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert

Meeting


The result of the new study on melting point was evaluated in an addendum. But, in the list of end points the old values for the melting point are still given. Thus, the list of end points has to be amended by the RMS.

Open point fullfilled. New open point 1.8: RMS to include the results of the new study on melting point in the list of end points.


The result of the new study on boiling/ decomposition point was evaluated in an addendum. But, in the list of end points the old values for the boiling/ decomposition point are still given. Thus, the list of end points has to be amended by the RMS.

Open point fullfilled. New open point 1.9: RMS to include the results of the new study on boiling/ decomposition point in the list of end points.


The storage stability test is still ongoing. Therefore, the data have to be awaited and the data requirement is still open. The meeting agreed that further data is necessary regarding the NDPA content after storage. Therefore, a new data requirement was confirmed by the meeting.

Data requirement is still open. New data requirement 1.6: Notifier to submit data about the content of NDPA after storage.


77/130



The RMS had evaluated the new shelf life study in an addendum and stated in the evaluation table that the study was not conducted under GLP. Therefore, the RMS propose that the notifier has to justify why the study was not conducted under GLP. Since no representative of the RMS attended the meeting. The meeting agreed that this point is still open.

This open point is still open. See data requirement 1.1


The procedures for cleaning equipment have been included in an addendum. Therefore, the meeting agreed that this data requirement is fulfilled.



The information on the effectiveness of cleaning procedures have been included in an addendum Therefore, the meeting agreed that this open point is fulfilled.

Open point fulfilled.


The information on transport (Road & Rail, Sea and Air) have been included in an addendum. Therefore, the meeting agreed that this open point is fulfilled.



78/130



The notifier gave a statement in the evaluation table on the LOQ values for the method of analysis. The RMS was satisfied with the notifier’s comment and proposedthat no further data is required. The meeting agreed that the data requirement is fulfilled. Note of the meeting. The LOQ belongs to the lowest fortified level.



The new analytical method for the determination of the a.s. in the lead formulation has been evaluated in an addendum and was proposed to be acceptable by the RMS. Therefore, the meeting agreed that this new method is acceptable. Thus, the open point is fulfilled.



The new analytical method for the determination of the Di-n-propyl-nitrosoamine in the lead formulation has been evaluated in an addendum. The RMS proposed in the addendum that the method is acceptable and adequately. Therefore, the meeting agreed that this method is acceptableand the open point is fulfilled.



79/130



The data requirement is still open and needs to be clarified by the ecotoxicological expert meeting. The meeting agreed that depending on the outcome of the discussion in the ecotoxicological expert meeting the analytical methods are required for TR-4 for determination in soil

Data requirement still open. Depending on the outcome of the discussion in the ecotoxicological expert meeting fully validated methods are required for TR-4 determination in soil. Note from EPCO 6 to EPCO 8: If the EPCO 8 decides that the metabolite TR-4 is included in the residue definition for soil, fully validated analytical methods determining this metabolite in soil will be required.


80/130



The data requirement is still open and needs to be confirmed by the ecotoxicological expert meeting. The meeting agreed that depending on the outcome of the discussion in the ecotoxicological expert meeting the analytical methods are required for TR-6 and TR-15 for determination in water.

Data requirement still open. Depending on the outcome of the discussion in the ecotoxicological expert meeting fully validated methods are required for TR-6 and TR-15 determination in water. Note from EPCO 6 to EPCO 8: If the EPCO 8 decides that the metabolites TR-6 and TR-15 are included in the residue definition for water, fully validated analytical methods determining this metabolite in soil will be required.

Evaluation table Trifluralin (Hb) EU RESTRICTED 16395/EPCO/BVL/04 rev. 0-2 (15.06.04) section 1 - Physical and Chemical properties

81/130

Appendix 2: Evaluation table 1. Physical and Chemical Properties No.







No comment The melting point of pure trifluralin is 47.2±0.1 oC (see Addendum to the DAR). No further data are required.

EPCO 6 (15.-16.06.2004): Open point fullfilled.

Open point 1.8: RMS to include the results of the new study on melting point in the list of end points. This new open point was proposed at the EPCO 6 Meeting.


82/130

No.






No comment The boiling point of pure trifluralin is not determinable due to decomposition. The decomposition temperature is 202±1 oC (see Addendum to the DAR). No further data are required.

EPCO 6 (15.-16.06.2004): Open point still open. RMS to include the result of the new study on boiling/ decomposition point in the list of end points.

Open point 1.9: RMS to include the results of the new study on boiling/ decomposition point in the list of end points. This new open point was proposed at the EPCO 6 Meeting.


This report will be available for submission by the end of April 2004.

The RMS took notice that the 2-year storage stability study will be completed and available for submission by the end of April 2004.

EPCO 6 (15.-16.06.2004): Data requirement is still open.

1.6 Notifier to submit data about the content of NDPA after storage. This new data requirement was proposed at the EPCO 6 Meeting.

EPCO 6 (15.-16.06.2004): Data requirement still open.


83/130

No.






No comment The purpose of the study submitted (Vorhies S., 2003) was to demostrate that the content of impurity N-nitroso-di-n-propylamine (NDPA) in the p.p.p. does not exceed the FAO specified limits throughout the shelf-life period. The data showed that the NDPA content remains at least 50% below the FAO specification limit, even after 2 years of storage (see Addendum to the DAR). The notifier should justify why the study was not conducted under GLP.

EPCO 6 (15.-16.06.2004): Open point still open. See data requirement 1.1


Advice for cleaning equipment is usually contained either on the product label or in leaflets. If this is not the case, procedures which have been supplied to the RMS and will be included in an addendum (see Open Point 1.4 should be followed. Alternatively, techniques which follow good agricultural codes of conduct may be employed.

Information on procedures for cleaning application equipment has been included in the addendum of the DAR.



84/130

No.






No comment Information on the effectiveness of cleaning procedures has been included in the addendum of the DAR.

EPCO 6 (15.-16.06.2004): Open point fulfilled.


No comment Information on transport (Road & Rail, Sea and Air) has been included in the addendum of the DAR.



85/130

No.






We agree that the reported ”limit of determination” (0.05%) and calculation of LOQ provided in response to initial DAR comments do not satisfy the definition of LOQ as defined in the SANCO guidance document. For the study in question, precision and accuracy was tested for each impurity (DAR Tables B.5.1.2.1 and B.5.1.2.2). Precision was tested at or near the range of the recovery concentrations (0.10 and 1.00 % w/w), which permit the precision and recovery data to be evaluated jointly. The LOQ may be set as the greater of the concentrations tested for those requirements. For example, precision of impurity 1 was tested at 1.24 % w/w and acceptable recovery was found at 1.0 % w/w; therefore, the LOQ for impurity 1 is 1.24 % w/w. Likewise, LOQ for impurities 2-6 are 0.10, 0.10, 0.15, 0.33, and 0.10, respectively. Each LOQ value is less than the maximum content for the respective impurity.

RMS is satisfied with notifier’s comment. LOQ values for the method of analysis for impurities of trifluralin technical are confirmed and are considered adequately low with regard to the specified maximum content of each impurity. No further data are required.



86/130

No.






No comment The evaluation of the new analytical method for the determination of the a.s. in the lead formulation EF-1521 has been included in the Addendum of the DAR. The method is acceptable, adequately validated.



No comment The evaluation of the new analytical method for the determination of the relevant impurity di-n-propyl-nitrosoamine in the lead formulation EF-1521 has been included in the Addendum of the DAR. The method is acceptable, adequately validated.



87/130

No.






We believe that the additional ecotoxicity studies for TR-4 that have been submitted have demonstrated that this metabolite is not relevant and so it should not be included in the residue definition for soil. Therefore, a validated analytical method for the determination of TR-4 in soil should not be required. However, if the RMS does not agree with this conclusion, a method will be developed and validated but until this requirement is confirmed a date for its availability cannot be provided.

RMS accepts the notifier’s comment. No analytical method for the determination of the metabolite TR-4 in soil is required, since it is not included in the residue definition for soil.

EPCO 6 (15.-16.06.2004): Data requirement still open. Depending on the outcome of the discussion in the ecotoxicological expert meeting fully validated methods are required for TR-4 determination in soil.


88/130

No.






We believe that the additional ecotoxicity studies for TR-6 and TR-15 that have been submitted have demonstrated that this metabolite is not relevant and so it should not be included in the residue definition for water. Therefore, validated analytical methods for the determination of TR-6 and TR-15 in water should not be required. However, if the RMS does not agree with this conclusion, methods will be developed and validated but until this requirement is confirmed a date for their availability cannot be provided.

RMS accepts the notifier’s comment. No analytical methods for the determination of the metabolites TR-6 and TR-15 in water are required, since they are not included in the residue definition for water.

EPCO 6 (15.-16.06.2004): Data requirement still open. Depending on the outcome of the discussion in the ecotoxicological expert meeting fully validated methods are required for TR-6 and TR-15 determination in water.

Message from EPCO 6 to EPCO 8: If the EPCO 8 decides that the metabolite TR-4 is included in the residue definition for soil, fully validated analytical methods determining this metabolite in soil will be required.


89/130

No.





Message from EPCO 6 to EPCO 8: If the EPCO 8 decides that the metabolites TR-6 and TR-15 are included in the residue definition for water, fully validated analytical methods determining this metabolite in soil will be required.



List of representative uses evaluated*

Trifluralin 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


PHI (days)

(l)

Remarks:

(m) Type

(d-f)

Conc. 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



EC 480 g/L

BI Pre A/S 1 NA 0.08-0.8 150-600 0.48-1.2 NA



EC 480 g/L

BI Pre S 1 NA 0.08-0.8 150-600 0.48-1.2 NA



EC 480 g/L

BI Pre S 1 NA 0.08-0.48

200-600 0.48-1.2 NA



EC 480 g/L

BS Pre A 1 NA 0.096-0.74

150-600 0.576-1.2

NA




EPCO Expert Meeting 08 16705/EPCO/BVL/04 trifluralin 22 June 2004

91/130

REPORT OF EPCO EXPERT MEETING TRIFLURALIN Rapporteur Member States: Greece 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:

none


Date Supplier File Name 22 December 2003 RMS/Greece Trifluralin consultation report 09 January 2004 RMS/Greece Trifluralin end points 04 February 2004 RMS/Greece Trifluralin reporting table rev1-1 March 2004 RMS/Greece Trifluralin addendum 2 vol3 March 2004 RMS/Greece Trifluralin addendum vol1 15 June 2004 RMS/Greece Trifluralin_evaluation_table_rev0-

3_ecotox_(15-06-2004) 15 June 2004 RMS/Greece Trifluralin end points ecotox June

2004 15 June 2004 RMS/Greece Trifluralin Addendum 3 to volume 3-

June 2004 3. Documents tabled at the meeting

Date Supplier File Name 22 June 2004 RMS/Greece Trifluralin evaluation table rev 0.3

ecotox 22 June 2004 RMS/Greece Trifluralin Table 9.2.8-01 Acute

toxicity to aquatic organisms and B.9.2.3 Bioaccumulation in fish

22 June 2004 RMS/Greece Trifluralin List of endpoints – Impact on Human and Animal Health

The conclusions of the meeting were as follows: 4. Data on preparations: EF1521. 5. Classification and labelling: N, R50/53 6. Recommended restrictions/conditions for use:


92/130

Areas of concern: Risk mitigation measures to protect aquatic life must be set on member state level. Appendix 1: EPCO discussion table: TRIFLURALIN Appendix 2: Evaluation table


93/130

Appendix 1: Discussion Table, Trifluralin (Hb) 5. Ecotoxicology No. Subject Discussion EPCO Expert Meeting Conclusions EPCO Expert

Meeting

New open point List of intended uses

The list of intended uses has to be revised in that way that it is clear that all application are pre-emergence applications. (The revised GAP were sent to EFSA prior the meeting but wasn’t uploaded on CIRCA and resent again in the new evaluation table presented by the RMS during the meeting later as electronic version to EPCO-Team. There is nothing more to add so we consider this open point as fulfilled. All application are pre-emergence)

New open point The list of intended uses has to be revised in that way that it is clear that all application are pre-emergence applications.


RMS: There is low toxicity to birds. EFSA: The TER for earthworm eating birds is unclear. RMS used worst case soil residues after 14 years and the immediate following application. Considering plateau concentration after 14 years in accordance with the guidance document would lead to a TER of 5.6 indicating an acceptable risk.



RMS: the calculated values are above the trigger values and the point is fulfilled Meeting agrees on this.



RMS: Acute toxicity: The most sensitive species are fishes. Thus the risk assessment was based on fishes. The 15 m buffer zone should become relevant in the area of concern. RMS: The NOT submitted lots of data to chronic toxicity concerning different live stages. Endpoints are all measured concentrations. MS refers to a summary table which was presented at the meeting for internal use. Meeting: Unfortunately the data package was generated over the last 20 years and the data are not always consistent (e.g. choice of test species). Trifluralin was

New data requirement: The initial PEC’s together with the NOEC of 0.3 µg/L should be used for a new risk assessment. If the notifier disagrees on this,, additional studies with different exposure regimes to identify the most critical exposure period should be conducted


94/130



measured in a monitoring study in ponds after runoff events which is indicative for a remobilisation from soil particles and vertebral lesions were determined in fish. A clear dose/response relationship could not be demonstrated but this is typical for such type of monitoring studies. Residue levels in fish should not be used to evaluate occurrence of vertebral lesions in fish because a residue level in a special point in time may not reflect the exposure profile over a longer time period. Although this effect was also observed in controls ( alachlor was used around this pond) there is clear evidence - also from other laboratory studies - that this active - at least partly - exerts this vertebral lesions. In a laboratory study under flow-through conditions especially designed to investigate this effect a NOEC of 0.3 µg/L was determined. Taking into account the fast degradation of trifluralin in water/sediment systems it is clear that a time weighted PEC should in principal be used for the risk assessment. However, in deciding upon the most relevant time period for this calculation “time to event” considerations must be considered. This special type of effects was also observed in a further study where fish were exposed for 24 hours in a static system where a clear dose response curve was observed but the NOEC was approximately 100 times higher. There are no other information available to decide upon the most appropriate period for PECtwa calculations. There is a need to conduct a new exposure assessment using FOCUS step 3 scenarios. No further testing is required if initial PECs are calculated. The aforementioned NOEC together with an uncertainty factor of 10 should be used for conducting the risk assessment. In this case the risk is unacceptable. It should be noted that one participant questioned the use of PECtwas in case of a compound with such a high BCF in general . The as bioconcetrates but the bioaccumulation problem was addressed because the as has a high clearance time. However if time weighted PECs should be used – and the meeting regarded this as a possible approach - more information is needed to identify the critical exposure period. Therefore flow-through tests with different exposure periods and fathead minnow should be conducted. As an alternative microcosm tests with a more realistic exposure regime may be run. The toxicity values from such a test should be used together with initial PECs.

be conducted. Notifier to submit exposure studies with different exposure times using the fathead minnow as the most sensitive fish species. Or another higher tier test (maybe mesocosm studies) can be conducted.


95/130



List of endpoints were redrafted. Open point fulfilled.


RMS: EPCO 3 asked EPCO 4 to present a population relevant toxicity value. The relevant end points are LD50> 5000 (mg as/kg b.w.) for acute and of 148 mg/kg bw/day, for long term toxicity, which would be relevant to population level effects. A discussion aroused why the other end point was disregarded. The reason for that should be mentioned in the report of the EPCO 4 meeting. Probably the lower toxicity value was based on a minor reversible histopathological effect. Nevertheless, this new end point is regarded as the relevant end point for populations and was accepted by the meeting.



The data have been evaluated in an addendum and the RMS has considered this open point as fulfilled. The TER long term of 4.44 (see also the addenda 3) was already accepted by EPCO 3: Therefore this open point is regarded as fulfilled.



96/130



RMS: TR4 is only represented in soil in anaerobic conditions and in sediment. In all cases (earthworm, sediment dwellers and micro-organism) toxicity values indicate no risk. Therefore TR4 is not regarded as relevant for the environment.

Open point fulfilled. New open point: RMS to revise residue definition for soil and sediment in the list of endpoints.


97/130



New water sediment study was submitted. The RMS regarded the toxicity of the metabolites TR14 & TR7 as comparable with the parent compound and stated that this is acceptable. Furthermore toxicity data on other metabolites are available which show that they are less toxic than the active. MS: If the metabolites belong to different groups of substances the result is not reliable, because they may behave different as the parent compound. Even 29.5 % of the TR14 were identified in the second sediment study. No toxicity studies are available. The QSAR approach is usually not relevant for major metabolites but here are toxicity data on other metabolites available. Therefore such an approach can be used in this special case The validity of the QSAR-calculations is difficult to evaluate because a considerable number of models and approaches are available. However, UK-PSD sponsored a research project on metabolites and a – at least partly – validated QSAR model came out of this project. If the part of the molecule relevant for the pesticide activity has been removed and the QSAR calculations with both metabolites show – confirmed by the project leader of the PSD-project or another independent organization or authority – a lower toxicity than the active no further testing is needed. As an alternative tests with sediment dwellers might be appropriate. Discussion at the meeting concerned not only comparison of metabolites TR14 & TR7 with active substance, but first of all comparison of these metabolites with metabolites TR4 & TR15 and the assumption of their similar toxicity. Comments mentioned at the meeting concerned the difference in functional group between metabolites TR14 & TR7 and TR4 & TR15.

Data requirement: The Notifier should submit further data on toxicity about the metabolites TR14 & TR7 using the PSD model or from another independent organization or authority based on the QSRA approach from Allister. Open point: The RMS should contact PSD regarding the QSAR-approach New open point: Residue definition for sediment needs to be revised pending on the outcome of data requirement x with regard to the metabolites TR14 and TR7.


Fulfilled Open point fulfilled.


Fulfilled Open point fulfilled.


98/130



The photolysis study seems to be highly unrealistic. Nevertheless, the toxicity values seem to be sufficient to decide upon the metabolites. Based on the risk assessment these two metabolites are not considered to be relevant for the environment. Therefore, the point was regarded to be fulfilled.

Open point fulfilled. New open point: RMS to revise residue definition for water in the list of endpoints.


See open point 5.3 Open point fulfilled.

New open point Message from EPCO5 1.4 If it is decided that the metabolite TR-4 is included in the residue definition for soil, fully validated analytical methods determining this metabolite in soil will be required.

See open point 5.7 Open point fulfilled.


99/130


New open point Message from EPCO5 1.5 If it is decided that the metabolites TR-6 and TR-15 are included in the residue definition for water, fully validated analytical methods determining these metabolites in water will be required.

See open point 5.10


MS did not have any other remarks on the list of endpoints than the remarks already mentioned above.


100/130

Appendix 2: Evaluation table 5. Ecotoxicology No.







.

ti d

The risk assessment has been revised strictly in accordance with the latest version of SANCO/4145/2000 and sent to the RMS for inclusion in the DAR. At tier 1, TERa values range from >35 to >283, TERst values range from 16 to 72 and TERlt values range from ≥2.8 to ≥13. The only TER value below its Annex VI trigger is the TERlt of 2.8 for insectivores. Based on a realistic exposure, this is refined to ≥5.9

29-March-04 Trifluralin risk assessment for Birds and Mammals according to Sanco/4145/2000. The relevant end points are LD50> 2250 (mg as/kg b.w.) for acute, 573.9 (mg as/kg bw/day) for short term and NOEC=102.85 mg as/kg bw/day for long term toxicity considering that the product is applied once on bare soil. The relevant RUD for acute toxicity a. for soil-dwelling insects is 1 (90%) and for short and long term toxicity is 0,1 (50%) (Aldenberg and Jaworska (2000) according to the Guidance Document on Risk Assessment for Birds and Mammals, Appendix II-9, Table 10 or b. 14 for acute toxicity and 5,1 for short and long term toxicity (large insects). Applications of trifluralin

EPCO 3 (28.-29.04.2004): Open point still open. RMS to present a revised risk assessment in the form of an Addendum.. EPCO 8 (22.-23.06.2004): Open point fulfilled.


101/130

No.






ti d

are made pre-emergence to bare soil. Larger, ground-dwelling insects are therefore the likely food item for birds. TER 1 risk assessment for leafy crop and cereals: Acute risk assessment The TER values for insectivorous bird are a. >1802 (RUD=1), b. >129 (RUD=14). The TER value for earthworm eating bird is >122 and for fish eating bird is >283. Short-term risk assessment The TER values for insectivorous bird are a. 4591 (RUD=0,1), b. 90 (RUD=5,1). The TER value for earthworm eating bird is 31 and for fish eating bird is 72. All of these TERA and TERST values exceed the Annex VI trigger value of 10. Long-term risk assessment The TER values for insectivorous


102/130

No.






bird are a. >822 (RUD=0,1), b. >16,1 (RUD=5,1). The TER values for earthworm eating bird is >5,6 and for fish eating bird is >13. All of these TERLT values exceed the Annex VI trigger value of 5. June 2004 Trifluralin risk assessment for Birds and Mammals according to Sanco/4145/2000. The relevant end points are LD50> 2250 (mg as/kg b.w.) for acute, 573.9 (mg as/kg bw/day) for short term and NOEC=102.85 mg as/kg bw/day for long term toxicity considering that the product is applied once on bare soil. The relevant RUD for acute toxicity for soil-dwelling insects is 14 and for short and long term toxicity 5.1 (large insects). Applications of trifluralin are made pre-emergence to bare soil. Larger, ground-dwelling insects are therefore the likely food item for birds. Tier 1 risk assessment:


103/130

No.






Acute risk assessment The TER value for insectivorous bird is >129, for earthworm eating bird is >59.9 and for fish eating bird is >283. Short-term risk assessment The TER value for insectivorous bird is 90, for earthworm eating bird is 15.28 and for fish eating bird is 72. All of these TERA and TERST values exceed the Annex VI trigger value of 10. Long-term risk assessment The TER value for insectivorous bird is >16,1, for earthworm eating bird is >2.74 and for fish eating bird is >13.

All of these TERLT values exceed the Annex VI trigger value of 5 except the risk on earthworms. Actually the NOEC used for the risk assessment was the highest concentration tested with the worst DT50 value. In addition the PECsoil used is the max theoretical accumulation plateau reached after 14 years! which seems unrealistic. According to fate and behaviour also in


104/130

No.






an accumulation study in UK trifluralin does not accumulate in soil following successive applications. This results to a refine TER ≥ 5.58. There is no consideration of the likely abundance of earthworm eating birds to feed exclusively for long periods on earthworms as the only relevant diet carrying only maximum residue levels. Consequently there are no unacceptable long-term risks for birds feeding on insects, earthworms and fish.


See above. The TER values based on a 1 m “no-spray zone are TERa >283, TERst 72 and TERlt ≥13.

29-March-04 See above. TER 1 risk assessment for leafy crop and cereals on a 1 m “no-spray zone”: Acute risk assessment The TER value for fish eating bird is >283. Short-term risk assessment The TER value for fish eating bird is 72. All of these TERA and TERST values exceed the Annex VI trigger value of 10. Long-term risk assessment

EPCO 3 (28.-29.04.2004): Open point still open. RMS to present a revised risk assessment in the form of an Addendum.. EPCO 8 (22.-23.06.2004): Open point fulfilled.


105/130

No.





continued Open point 5.2: RMS to revise the risk assessment for fish eating birds in an addendum.

The TER values for fish eating bird is >13. This TERLT value exceed the Annex VI trigger value of 5. June-04 See above.


The chronic risk assessment has been conducted assuming (i) continuous exposure to the TWAC and (ii) episodic exposure to a peak concentration plus an extensive development period. The TERlt values are 13 and 11, respectively, providing the 5 m “no-spray” zone is observed. Additional risk assessments for the metabolites of trifluralin have been sent to the RMS for inclusion in the DAR.

29-March-04 According to fate & behaviour data trifluralin readily adsorbs to sediments and dissipation from the water column will be rapid (DT50 ca. 6 hours). Consequently, exposure in the field will be characterised by a brief exposure to relatively high concentrations, followed by rapid dissipation. The rapid dissipation by itself is a strong argument for not conducing long term trials. It is possible to refine the chronic risk to fish according to two different scenarios i.e. (i) a continuous exposure to low concentrations and (ii) a brief exposure to peak concentrations followed by a prolonged developmental period. Continuous exposure to low

EPCO 3 (28.-29.04.2004): Open point still open. RMS to present revised risk assessment as an Addendum. EPCO 8 (22.-23.06.2004): Open point fulfilled. See new data requirement 5.1


106/130

No.






concentrations Due to the rapid dissipation of trifluralin in water, it is appropriate to refine the chronic risk by comparing the 35 day chronic NOEC of 0.3 µg as/L with the 35-day TWA concentrations based on the DT50 of ca. 6 hours. The refined TERlt values based on chronic exposure are 2,6 and 13 (at 1 and 5 m “no-spray” zones). According to these TERlt values, based on chronic exposure, there would be no unacceptable long-term risks for fish, providing a minimum “no-spray” zone of 5 m. Brief exposure to peak concentrations The chronic risk assessment for fish is refined using the 24-hour NOEC of 25 µg/L (24h exposure plus 1 year development period). The refined TERlt values are 2 and 11 (at 1 and 5 m “no-spray” zones). The Annex VI minimum TERLT of 10 is met with a “no-spray” buffer zone of 5 m. June 2004 Acute toxicity


107/130

No.






For acute toxicity a 15 m “no-spray-zone” would be required to reduce the risk for the parent compound for the Annex VI trigger values of 100 and 10 respectively, as a “tier 1 level” risk assessment. For the photodegradation products, TR-6 and TR-15 even in the absence of a “no-spray” zone, and assuming maximum possible formation rates, all TERa values exceed the Annex VI triggers of 100 (fish and Daphnia) and 10 (algae). The impact of photolysis on the degradation of trifluralin in water is not expected to be the same for all the Member States. A more realistic exposure scenario is that the amounts of these two major photoproducts will be reduced under actual use conditions. Chronic toxicity According to the Descussion Table from EPCO 3 the meeting commented that RMS should propose NOECs for both growth and survival. From information summarised in fate section, parent trifluralin


108/130

No.






appears to dissipate rapidly from the water phase due to adsorption to sediment and photolysis. This comes in agreement with the field monitoring data. Consequently, exposure in the field will be characterised by a brief exposure to relatively high concentrations, followed by rapid dissipation. It is possible to refine the chronic risk to fish according to two different scenarios i.e. (i) a continuous exposure to low concentrations and (ii) a brief exposure to peak concentrations followed by a prolonged developmental period. Continuous exposure to low concentrations Due to the rapid dissipation of trifluralin in water, it is appropriate to refine the chronic risk by comparing the 48 day chronic NOEC of 1.14 µg as/L with the twa PECsw according to SANCO/3268/2001, Point 3.3. The refined TERlt values based on chronic exposure are 1.78 and 16.28 (at 1 and 10 m “no-spray” zones).


109/130

No.






Brief exposure to peak concentrations The chronic risk assessment for fish is refined using the 24-hour NOEC of 25 µg/L (24h exposure plus 1 year development period). The refined TERlt values are 2 and 11 (at 1 and 5 m “no-spray” zones). It should be emphasized that the strong tendency of trifluralin (Koc 6400-13400 lt/kg) to adsorb to soil, sediment and suspended matter significantly reduces toxicity risks in the water phase, because trifluralin will hardly be present here. In addition there was no opportunity for biomagnification to occur through the food chain. This is in agreement with the proposal prepared by the Fraunhofer Institute for trifluralin. According to the chemical and fate profile of the substance the chronic laboratory exposure of the parent compound produced is not likely to occur in real conditions (continues exposure for more than 35 d for an unstable substance). Given the worst-case nature of the initial


110/130

No.






PECsw calculations it is likely that the use of trifluralin as recommended will not lead to unacceptable impacts on fish populations with a requirement for further risk mitigation measures (e.g. buffer zones) at Member State level. For sediment organisms the risk from the parent compound and the metabolites is considered to be low on the basis of their similarity to the previously tested metabolites. TR-7 is structurally similar to TR-4 and TR-14 is structurally similar to TR-15. Since all three metabolites tested to date are less toxic than the parent, trifluralin, and formed in lower amounts, then the risk from TR-7 and TR-14 is also likely to be low.


111/130

No.






See Open Point 5.1. All TERst and TERlt values now based on “daily dose”.

29-March-04 The relevant end points are LD50> 2250 (mg as/kg b.w.) for acute, 573.9 (mg as/kg bw/day) for short term and NOEC>102.85 mg as/kg bw/day for long term toxicity. All these values are included in the revision of the list of end-points. June 2004 See above

EPCO 3 (28.-29.04.2004): Open point still open. To be revised after MamTox meeting. Action EFSA/RMS to ensure that MamTox EPCO 4 meeting is asked to provide an appropriate repro. NOEC. EPCO 8 (22.-23.06.2004): Open point fulfilled.


The risk assessment has been revised in accordance with SANCO/4145/2000 and sent to the RMS for inclusion in the DAR. At tier 1, TER values range from TERa >87 to >187 and TERlt 2.8 to 2.2. The TERlt values have been refined and exceed the Annex VI trigger for insectivores and fish-eating species. In order to refine the risk to mammals eating earthworms, however, actual residue data are required.

29-March-04 The relevant end points are LD50> 5000 (mg as/kg b.w.) for acute and NOAEL for kidney changes was 200 ppm, equivalent to a dosage of 10.7 mg/kg bw/day, for long term toxicity. The chronic LOAEC was 813 mg/kg, equivalent to a dosage of 30 mg/kg bw/day, based on renal transitional cell carcinoma in two male rats (3.4%) at this dosage. All these values are included in the revision of the list of end-points. Trifluralin risk assessment for Birds and Mammals according to Sanco/4145/2000 always considering that the product is applied once on bare soil. A di t th G id li

EPCO 3 (28.-29.04.2004): Open point still open. To be revised after MamTox meeting. Action EFSA/RMS to ensure that MamTox EPCO 4 meeting is asked to provide an appropriate repro. NOEC. EPCO 8 (22.-23.06.2004): Open point fulfilled.


112/130

No.






According to the same Guideline there is no exposure for insectivorous mammals for the proposed crops according to the GAP (i.e. “early application” to leafy crops or cereals). TER 1 risk assessment for leafy crop and cereals: Acute risk assessment The TER values for earthworm eating mammal is >39 and for fish eating mammal is >187. All of these TERA values exceed the Annex VI trigger value of 10. Long-term risk assessment The TER values for earthworm eating bird is 0,5 and for fish eating bird is 2,2. All of these TERLT values are below the Annex VI trigger value of 5. For mammals feeding on fish, exposure may be refined by considering the effect of the 5 m “no-spray” zone proposed to mitigate against adverse effects on aquatic organisms. The revised TERLT value is 11. Another option is to adopt the chronic LOAEC of 813 mg/kg (30 mg/kg bw/day) as the critical


113/130

No.






endpoint on the grounds that the incidence of renal transitional cell carcinoma was low at this dose (in two male rats only, equivalent to 3.4%) and that these renal tumours arose by a non-genotoxic mode of action and did not occur in female Fischer rats or in two other strains of rat or in mice. Revised TERLT values based on this endpoint are values for earthworm eating bird is 1,3 and for fish eating bird is 6,1. According to this approach, there would be no unacceptable long-term risks for mammals feeding on fish, but the high theoretical residue levels predicted for earthworms would still indicate a cause for concern. An alternative approach would be to refine the exposure. As in the avian risk assessment, long-term exposure to residues is most likely to occur from earthworms absorbing residues from soil-incorporated trifluralin (any material remaining on the soil surface would be rapidly photolysed, thereby removing the risk of long-term exposure). The highest risk indicated from the TER values above appears to come from earthworms and this would also be anticipated from the likelihood of uptake from soils, given the more permeable


114/130

No.






nature of the earthworm cuticle. Consequently, actual residue levels determined in earthworms exposed to trifluralin-treated soil could be used to refine the long-term risk assessment for mammals consuming earthworms. It is recommended, therefore, that the Notifier generates such data. June 2004 The relevant end points are LD50> 5000 (mg as/kg b.w.) for acute and of 148 mg/kg bw/day, for long term toxicity according to the results from EPCO 3 (ecotoxicology meeting) and EPCO 4 (toxicology meeting). All these values are included in the revision of the list of end-points. Trifluralin risk assessment for Birds and Mammals according to Sanco/4145/2000 always considering that the product is applied once on bare soil. According to the same Guideline there is no exposure for insectivorous mammals for the proposed crops according to the GAP (i.e. “early application” to leafy crops or cereals). Tier 1 risk assessment: Acute risk assessment The TER values for insectivorous

l i 87 f th


115/130

No.






mammal is >87, for earthworm eating mammal is >19.22 and for fish eating mammal is >187. All of these TERA values exceed the Annex VI trigger value of 10. Long-term risk assessment The TER values for insectivorous mammals is 38.38, for earthworm eating bird is 3.09 and for fish eating bird is 30. All of these TERLT values exceed the Annex VI trigger value of 5 except the risk on earthworms. The PECsoil used is the max theoretical accumulation plateau reached after 14 years! which seems unrealistic. According to fate and behaviour also in an accumulation study in UK trifluralin does not accumulate in soil following successive applications. This results to a refine TER ≥ 6.31. There is no consideration of the likely abundance of earthworm eating mammals to feed exclusively for long periods on earthworms as the only relevant diet carrying only maximum residue levels. Consequently there are no unacceptable long-term risks for mammals feeding on insects, earthworms and fish.


116/130

No.






ti d

The risk assessment has been revised in accordance with SANCO/10329/2002 and sent to the RMS for inclusion in the DAR. Tier 1 TERa values are >313, 484 and >150 for the active substance, its metabolite TR-4 and its formulated product EF-1521, even when the correction factor of 0.5 is applied. The tier 1 TERlt of 3.0 is revised to 9.1 when re-calculated according to SANCO/10329/2002.

29-March-04 The LC50 values multiplied by the correction factor of 0.5 (to account for the high organic carbon content of the OECD soil), will lead to the lowest possible TERA or TERLT values. TER 1 risk assessment: Acute risk assessment The TER values for acute toxicity are >313 for trifluralin and >150 for the formulation. All of these TERA values exceed the Annex VI trigger value of 10. Long-term risk assessment The TER value for long term toxicity is > 3 for the formulation. This value is below the Annex VI trigger value of 5. No adverse effects on earthworm survival, growth or reproduction were observed at a treatment rate equivalent to 7,200 g as/ha (9.6 mg as/kg). In the sub-acute study (Ref. MJ15) the test material was applied at the maximum rate of 15 L product/ha (7245 g as/ha). Since the vessels had a surface area of 200 cm2 and

EPCO 3 (28.-29.04.2004): Open point still open. RMS to highlight that earthworm NOEC has been modified to take account of the logkow in the endpoint table (e.g NOECcorr) RMS to include revised risk assessment in an Addendum.. EPCO 8 (22.-23.06.2004): Open point fulfilled.


117/130

No.





continued Open point 5.6: RMS to revise the risk assessment for earthworms in an addendum.

contained 500 g dry weight of soil, the actual treatment in the study was equivalent to 28.98 mg as/kg dry soil. This NOEC is then adjusted to 14.49 mg as/kg dry weight by applying the factor of 0.5 (to allow for the high organic carbon content of the soil) and compared to the PECS. The revised TERlt is ≥ 9.1, which confirms that there is no unacceptable long-term risk to earthworms. June 2004 The LC50 values multiplied by the correction factor of 0.5 (to account for the high organic carbon content of the OECD soil), will lead to the lowest possible TERA or TERLT values. Tier 1 risk assessment: Acute risk assessment The TER values for acute toxicity are >153 for trifluralin, >74 for the formulation and 484 for the anaerobic metabolite TR-4. All of these TERA values exceed the Annex VI trigger value of 10.


118/130

No.





continued Open point 5.6: RMS to revise the risk assessment for earthworms in an addendum.

Long-term risk assessment The TER value for long term toxicity is > 4.44 for the formulation. This value is just below the Annex VI trigger value of 5. Actually the NOEC used for the risk assessment was the highest concentration tested with the worst DT50 value. In addition the PECsoil used is the max theoretical accumulation plateau reached after 14 years! which seems unrealistic but also results to TERlt > 4.44-8.88. According to fate and behaviour also in an accumulation study in UK trifluralin does not accumulate in soil following successive applications. According to EPCO 3 (ecotoxicology meeting) it was agreed that the risk assessment, based on a worst case scenario of exposure (being the maximum PEC plateau value of 3.26 mg as/kg after 14 years!), and a conservative NOEC (being the highest dose tested), was acceptable. Consequently there is no unacceptable long-term risk to earthworms.


119/130

No.






June 2004 1. Risk assessment sediment

dwellers metabolite TR4 The chronic toxicity study with the midge, Chironomus riparius, using spiked water in sediment:water exposure system has been determined to be 332.4 µg as/L (Trifluralin Addendum 2 to Volume 3). The TERA value of 124 is so far in excess of the Annex VI recommended trigger of 10. 2. Risk assessment soil metabolite

TR4 for earthworms The acute toxicity to earthworms of the metabolite TR-4 has been determined to be 186 mg/kg. The TERA value of 484 for acute exposure is so far in excess of the Annex VI recommended trigger of 10 and the acute risk to earthworms is low. 3. Risk assessment

microorganisms TR4. The effect of the soil metabolite TR-4 on soil micro-organism respiration and nitrogen turnover in two soil types has been determined in a study following OECD Guideline

EPCO 3 (28.-29.04.2004): Open point still open: RMS to insert data from TR4 into Endpoint Table. RMS to check risk assessment for TR4 and present as an Addendum. EPCO 8 (22.-23.06.2004): Open point fulfilled. See new open point 5.15:


120/130

No.





continued New open point 5.7 Extra info new data in addendum results in new risk assessments as follows: 1. Risk assessment sediment dwellers metabolite TR4 2. Risk assessment soil metabolite TR4 for earthworms 3. Risk assessment microorganisms TR4.

study following OECD Guideline Nos. 216 and 217 (Trifluralin Addendum 2 to Volume 3). In this study, the deviation from control values at the end of the 28/29 day study were -1.2% for respiration and +4.8% for nitrogen transformation rate. According to this finding, a soil concentration of TR-4 that is 10 times the PEC for this metabolite would have no adverse effects on soil microbial activity.


June 2004 Two new major metabolites were identified in the sediment layer, TR-7 and TR-14. Ecotoxicity data are not available for TR-7 and TR-14, since these metabolites have only recently been identified. However, the risk from these metabolites is considered to be low on the basis of their similarity to the previously tested metabolites. TR-7 is structurally similar to TR-4 with the -NO2 group replaced by a second -NH2 group and TR-14 is structurally

Open point still open. RMS to include risk assessment for TR14 and TR7 in an Addendum. EPCO 8 (22.-23.06.2004): Open point: The RMS should contact PSD regarding the QSAR-approach Open point was amended at the EPCO 8 Meeting. See new data requirement 5.2: See new open point 5.16


121/130

No.





continued New open point 5.8 Fate EPCO2 meeting identified 2 new metabolites TR14 & TR7.

similar to TR-15 with the same -NO2 group replaced by the -NH2 group plus the replacement of the -C3H7 by a single -H. Given that TR-6 and TR-15 have similar toxicities (and at least 10-times less toxic than trifluralin) and the TERA value of 124 for TR-4 is so far in excess of the Annex VI recommended trigger of 10 (open point 5.7), RMS doubt that these minor structural changes would make much difference to their toxicities i.e. they also would be significantly less toxic than the parent trifluralin. Since all three metabolites tested to date are less toxic than the parent, trifluralin, and formed in lower amounts, then the risk from TR-7 and TR-14 is also likely to be low. In order to demonstrate this, conservative TER values have been calculated based on their maximum formation rate but assuming that they are of the same toxicity as trifluralin. From the TER values it is evident that there would be no risk to sediment organisms


122/130

No.






June 2004 In the list oφ representatives uses evaluated the assessment includes pre-emergence applications in all cases

EPCO 3 (28.-29.04.2004): Open point still open. RMS to clarify GAP and amend GAP table if necessary. EPCO 8 (22.-23.06.2004): Open point fulfilled.


June 2004 A new evaluation table has been provided

EPCO 3 (28.-29.04.2004): Open point still open. RMS to produce revised Evaluation Table. EPCO 8 (22.-23.06.2004): Open point fulfilled.


123/130

No.






June 2004 Two metabolites through photolysis were found TR-6 and TR-15. However, the conditions of this study would be expected to maximise and facilitate photolysis, i.e. non-turbid, shallow water with no sediment present. A more realistic exposure scenario is that the amounts of these two major photoproducts will be reduced under actual use conditions. This will be due to the rapid partitioning of trifluralin from the water column to the sediment layer, as evidenced by the water/sediment study where application was made to the water layer. An estimate of these reduced exposure levels can be made by multiplying the maximum photolysis amounts observed for TR-6 and TR-15, i.e. 50.4% AR and 31.5% AR, by the maximum amount of total radioactivity found in the water column from the water/sediment study, i.e. 11% AR. This gives reduced anticipated exposure levels of 5.5% AR and 3.2% AR, respectively. Any relevance of photoproducts should

EPCO 3 (28.-29.04.2004): Open point still open. RMS to consider importance of photolysis and the ecological relevance of metabolites TR6 and TR15 in an Addendum. EPCO 8 (22.-23.06.2004): Open point fulfilled. See new open point 5.17


124/130

No.





continued New open point 5.11 from Fate EPCO 2 meeting (Arising from Open Point 4.1) TR6 and TR15 identified as surface water metabolites from the photolysis study.

be decided at MS level, since the impact of photolysis on the degradation of trifluralin in water is not expected to be the same for all the Member States. Specific risk assessments may also be conducted since there are data available for these metabolites. Even in the absence of a “no-spray” zone, and assuming maximum possible formation rates, all TERa values exceed the Annex VI triggers of 100 (fish and Daphnia) and 10 (algae).


June 2004 According to EPCO 2 (fate & behaviour) it was proposed that a DT50 of 13d in a worst case first tier PEC assessment and 2d based on a realistic worst case for refinement should be used. Even though the modelled half life may be most relevant, it might not reflect all possible situations and relevant environmental conditions and so, erring on the side of caution. The RMS object strongly to the use of the 13 day DT50. During the first water/sediment study, in the water

EPCO 3 (28.-29.04.2004): Open point still open. RMS to reconsider aquatic risk assessment taking the proposed DT50 of 13 days and revise Addendum as necessary. EPCO 8 (22.-23.06.2004): Open point fulfilled.


125/130

No.





continued New open point 5.12 from Fate EPCO 2 meeting (Arising from Open Point 4.3) a new sed/water DT50 value of 13 days.

phase of dark, adsorption to the sediment was so rapid that only 3-11%AR was measured within the first 6 hours. Although it is not possible to calculate a precise DT50 because of this, it is clearly evident that the DT50 is <6 hours. The proposal to refine the DT50 to 2 days, based on the new third water/sediment study, is also not appropriate. In this study, designed specifically to look at sediment metabolites and not partitioning of parent trifluralin, the material was added to the settled wet sediment and then water was added. It is not therefore a “water-spiked” study and the DT50 is not comparable (adding the water would have stirred up suspended sediment and given an artificially high initial reading compared with the standard method used in study 1).


126/130

No.





New open point 5.13 Message from EPCO5 1.4 If it is decided that the metabolite TR-4 is included in the residue definition for soil, fully validated analytical methods determining this metabolite in soil will be required.


New open point 5.14 Message from EPCO51.5 If it is decided that the metabolites TR-6 and TR-15 are included in the residue definition for water, fully validated analytical methods determining these metabolites in water will be required.


5.1 The initial PEC’s together with the NOEC of 0.3 µg/L should be used for a new chronic risk assessment for aguatic organisms. If the notifier disagrees on this, additional studies with different exposure regimes to identify the most critial



127/130

No.





exposure period should be conducted. Notifier to submit exposure studies with different exposure times using the fathead minnow as the most sensitive fish species. Or another higher tier test (maybe mesocosm studies) can be conducted. Data requirement was proposed in the EPCO 8 meeting.

5.2 The Notifier should submit further data on toxicity about the metabolites TR14 & TR7 using the PSD model or from another independent organization or authority based on the QSAR approach from Allister. Data requirement was proposed in the EPCO 8 meeting.



128/130

No.





New open point 5.15: RMS to revise residue definition for soil and sediment in the list of endpoints regarding metabolite TR4

EPCO 8 (22.-23.06.2004): Open point still open.

New open point 5.16: Residue definition for sediment needs to be revised pending on the outcome of data requirement 5.2 with regard to the metabolites TR14 and TR7. New open point was proposed in the EPCO 8 meeting.


New open point 5.17: RMS to revise residue definition for water in the list of endpoints regarding metabolites TR6 and TR15. New open point was proposed in the EPCO 8 meeting.



129/130

No.





New open point 5.18 The list of intended uses has to be revised in that way that it is clear that all application are pre-emergence applications New open point was proposed in the EPCO 8 meeting.



130/130

List of representative uses evaluated* Trifluralin 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


PHI (days)

(l)

Remarks:

(m) Type

(d-f)

Conc. 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



EC 480 g/L

BI Pre A/S 1 NA 0.08-0.8 150-600 0.48-1.2 NA



EC 480 g/L

BI Pre S 1 NA 0.08-0.8 150-600 0.48-1.2 NA



EC 480 g/L

BI Pre S 1 NA 0.08-0.48

200-600 0.48-1.2 NA



EC 480 g/L

BS Pre A 1 NA 0.096-0.74

150-600 0.576-1.2

NA


BI = Broadcast spray to bare soil followed by incorporation into soil BS = Broadcast spray to bare soil without incorporation Pre = Pre-sowing pre-emergense Post = Post sowing pre-emergense A = Autumn , S= Spring, NA = Not applicable


PEER REVIEW REPORT ON TRIFLURALIN 04.04.2005 TABLE OF CONTENTS · PEER REVIEW REPORT ON TRIFLURALIN...

Documents

Transcript of PEER REVIEW REPORT ON TRIFLURALIN 04.04.2005 TABLE OF CONTENTS · PEER REVIEW REPORT ON TRIFLURALIN...