Conclusion on the peer review of the pesticide risk assessment of the active substance imazaquin 1

Transcription

1 CONCLUSION ON PESTICIDE PEER REVIEW Conclusion on the peer review of the pesticide risk assessment of the active substance imazaquin 1 European Food Safety Authority 2 European Food Safety Authority (EFSA), Parma, Italy SUMMARY Imazaquin is one of the 84 substances of the third stage part B of the review programme covered by Commission Regulation (EC) No 1490/2002, 3 as amended by Commission Regulation (EC) No 1095/ Imazaquin was included in Annex I to Directive 91/414/EEC on 1 January 2009 pursuant to Article 11b of the Regulation (EC) No 1490/2002, as amended by Commission Regulation (EC) No 1095/2007 (hereinafter referred to as the Regulation ). In accordance with Article 12a of the Regulation the European Food Safety Authority (EFSA) is required to deliver by 31 December 2010 its view on the draft review report submitted by the Commission of the European Communities (hereinafter referred to as the Commission ) in accordance with Article 12(1) of the Regulation. This review report was established as a result of the evaluation provided by the designated rapporteur Member State in the Draft Assessment Report (DAR). The EFSA therefore organised a peer review of the DAR. The conclusions of the peer review are set out in this report. Belgium being the designated rapporteur Member State submitted the DAR on imazaquin in accordance with the provisions of Article 10(1) of the Regulation, which was received by the EFSA on 4 January The peer review was initiated on 7 January 2008 by dispatching the DAR for consultation of the notifier BASF Belgium S.A., and on 21 January 2008 to the Member States for consultation and comments. Following consideration of the comments received on the DAR, it was concluded that there was no need to conduct a consultation with Member State experts and that EFSA should deliver its conclusions on imazaquin. The conclusions laid down in this report were reached on the basis of the evaluation of the representative uses of imazaquin as a plant growth regulator in winter wheat and winter barley to prevent lodging, as proposed by the notifier. Full details of the representative uses can be found in Appendix A to this report. Data gaps were identified in the physical and chemical properties section. 1 On request from the European Commission, Question No EFSA-Q , issued on 17 December Correspondence: praper@efsa.europa.eu 3 OJ L224, , p.25 4 OJ L 246, , p.19 For citation purposes: European Food Safety Authority; Conclusion on the peer review of the pesticide risk assessment of the active substance imazaquin.. [57 pp.]. doi: /j.efsa Available online: European Food Safety Authority, 2011

2 In the mammalian toxicology section no major data gaps were found in the context of the representative uses assessed. The consumer risk assessment for the representative use of imazaquin in wheat has been addressed by the available data. For the use in barley, residue trials are necessary to finalise the risk assessment (data gap). The data available on environmental fate and behaviour are sufficient to carry out the required environmental exposure assessments at the EU level for the representative uses assessed. The potential for groundwater exposure above the parametric drinking water limit of 0.1µg/L from these uses by imazaquin and the soil metabolite CL was assessed as low. No data gaps were identified in the section on ecotoxicology. KEY WORDS Imazaquin, peer review, risk assessment, pesticide, plant growth regulator. 2

3 TABLE OF CONTENTS Summary... 1 Table of contents... 3 Background... 4 The active substance and the formulated product... 6 Conclusions of the evaluation Identity, physical/chemical/technical properties and methods of analysis Mammalian toxicity Residues Environmental fate and behaviour Ecotoxicology Overview of the risk assessment of compounds listed in residue definitions triggering assessment of effects data for the environmental compartments Soil Ground water Surface water and sediment Air List of studies to be generated, still ongoing or available but not peer reviewed Particular conditions proposed to be taken into account to manage the risk(s) identified Issues that could not be finalised Critical areas of concern References Appendices Abbreviations

4 BACKGROUND Imazaquin is one of the 84 substances of the third stage part B of the review programme covered by Commission Regulation (EC) No 1490/2002, 5 as amended by Commission Regulation (EC) No 1095/ Imazaquin was included in Annex I to Directive 91/414/EEC on 1 January 2009 pursuant to Article 11b of the Regulation (EC) No 1490/2002, as amended by Commission Regulation (EC) No 1095/2007 (hereinafter referred to as the Regulation ). In accordance with Article 12a of the Regulation the European Food Safety Authority (EFSA) is required to deliver by 31 December 2010 its view on the draft review report submitted by the Commission of the European Communities (hereinafter referred to as the Commission ) in accordance with Article 12(1) of the Regulation (European Commission, 2008). This review report was established as a result of the evaluation provided by the designated rapporteur Member State in the Draft Assessment Report (DAR). The EFSA therefore organised a peer review of the DAR. The conclusions of the peer review are set out in this report. Belgium being the designated rapporteur Member State submitted the DAR on imazaquin in accordance with the provisions of Article 10(1) of the Regulation, which was received by the EFSA on 4 January 2008 (Belgium, 2007). The peer review was initiated on 7 January 2008 by dispatching the DAR for consultation of the notifier BASF Belgium S.A., and on 21 January 2008 to the Member States for consultation and comments. In addition, the EFSA conducted a public consultation on the DAR. The comments received were collated by the EFSA and forwarded to the rapporteur Member State for compilation and evaluation in the format of a Reporting Table. The comments were evaluated by the rapporteur Member State in column 3 of the Reporting Table. The scope of the peer review was considered in a telephone conference between the EFSA, the rapporteur Member State, and the Commission on 30 July On the basis of the comments received and the rapporteur Member State s evaluation thereof it was concluded that there was no need to conduct a consultation with Member State experts and EFSA should deliver its conclusions on imazaquin. The outcome of the telephone conference, together with EFSA s further consideration of the comments is reflected in the conclusions set out in column 4 of the Reporting Table. All points that were identified as unresolved at the end of the comment evaluation phase and which required further consideration, including additional information to be submitted by the notifier, were compiled by the EFSA in the format of an Evaluation Table. The conclusions arising from the consideration by the EFSA, and as appropriate by the rapporteur Member State, of the points identified in the Evaluation Table, together with the outcome of the written procedure with Member States on the points of clarification for the notifier, were reported in the final column of the Evaluation Table. A final consultation on the conclusions arising from the peer review of the risk assessment took place with Member States via a written procedure in October November This conclusion report summarises the outcome of the peer review of the risk assessment on the active substance and the representative formulation evaluated on the basis of the representative uses as a plant growth regulator in winter wheat and winter barley to prevent lodging, as proposed by the notifier. A list of the relevant end points for the active substance as well as the formulation is provided in Appendix A. In addition, a key supporting document to this conclusion is the Peer Review 5 OJ L224, , p.25 6 OJ L 246, , p.19 4

5 Report, which is a compilation of the documentation developed to evaluate and address all issues raised in the peer review, from the commenting phase to the conclusion. The Peer Review Report (EFSA, 2011) comprises the following documents: the comments received on the DAR, the Reporting Table (revision 1-1; 2 August 2010), the Evaluation Table (13 December 2010), the report of the written procedure with Member States on points of clarification. Given the importance of the DAR including its addendum (compiled version of October 2010 containing all individually submitted addenda; Belgium, 2010) and the peer review report, both documents are considered respectively as background documents A and B to this conclusion. 5

6 THE ACTIVE SUBSTANCE AND THE FORMULATED PRODUCT Imazaquin is the ISO common name for 2-[(RS)-4-isopropyl-4-methyl-5-oxo-2-imidazolin-2- yl]quinoline-3-carboxylic acid (IUPAC). The representative formulated product for the evaluation was Meteor a soluble concentrate (SL) containing 0.8 g/l imazaquin, 368 g/l chlormequat chloride and 28 g/l choline chloride. The choline chloride is reported to be a safener. The representative uses evaluated comprise outdoor foliar spraying in winter wheat and barley to prevent lodging. Full details of the GAP can be found in the list of end points in Appendix A. CONCLUSIONS OF THE EVALUATION It must be noted that imazaquin is a racemic mixture of isomers, but the possible preferential metabolism/degradation of each enantiomer in animals, plants and the environment was not investigated in the studies submitted in the dossier. This is also true of the transformation products that retain a chiral carbon. Moreover, the analytical methods used in the studies reported through all sections were not stereo-selective, and all values mentioned as imazaquin and CL have to be considered as sum of isomers. The possible impact of each individual enantiomer on the toxicity, the consumer risk assessment, worker exposure and the environment has however been considered in a qualitative way. Consequently a general data gap, applicable for sections 2, 3, 4 and 5, was identified to address the impact of the isomeric composition of the substance and CL However the additional uncertainty resulting from not having information on the behaviour of individual isomers is not considered to be of concern for the representative uses assessed, with the possible exception of the consumer risk assessment consequent to the use on barley. 1. Identity, physical/chemical/technical properties and methods of analysis The minimum purity of the active substance as manufactured is 960 g/kg. Imazaquin is a racemate. Hydrogen cyanide and toluene are considered relevant impurities but no maximum content can be set and data gaps have been identified. Consequently the specification should be regarded as provisional. The main data regarding the identity of imazaquin and its physical and chemical properties are given in Appendix A. In response to comments on the DAR the notifier stated that imazaquin is in the form of the ammonium salt in the formulation. This is achieved by the addition of ammonium hydroxide. However, the rapporteur highlighted that ammonium hydroxide is not in the formulation details. A data gap has been identified for the notifier to confirm the formulation details. It should be noted that imazaquin is not stable in the formulation and appropriate storage and labelling needs to be considered. Methods enabling determination of the content of the relevant impurities in the representative formulated products were not provided because these impurities will not increase on storage, however this may be required at Member State level, pursuant to Art. 4, 1(c) of Council Directive 91/414/EEC. Residues of imazaquin in plants can be analysed by HPLC-UV, however a data gap was identified for a confirmatory method. A method of analysis for products of animal origin is not required as no MRLs are proposed. Soil is analysed by LC-MS, but there is a data gap for additional validation of the confirmatory method. Water and air are both analysed by LC-MS with confirmation by LC-MS/MS. A method of analysis for body fluids and tissues is not required as the active substance is not classified as toxic or very toxic. 6

7 2. Mammalian toxicity The acute toxicity by oral route of imazaquin was moderate in the mouse (one study showed a LD 50 of 1752 mg/kg bw) and low in the rat. The classification as R22 Harmful if swallowed was proposed. Imazaquin is not an eye and skin irritant, or a skin sensitiser. Subchronic oral toxicity studies in the rat (90-day) and in the dog (1-year) were submitted. The dog was the most sensitive species, with a meaningful decrease of body weight in both sexes. Animals suffered slight reactive anaemia, with decreased red blood cells and concomitant bone marrow hypercellularity. Histopathology revealed skeletal muscle myopathy, supported by significantly increased creatinine phosphokinase and lactate dehydrogenase activities. Transaminase activity and total bilirubin levels were also increased at the top dose, associated with effects in the liver (liver weight was slightly increased, but with minimal histopathological findings). The No Observed Adverse Effect Level (NOAEL) was set at the mid dose of 25 mg/kg bw/day. Two long-term dietary studies were conducted in the rodents. The lowest relevant NOAEL was detected in the mouse at 150 mg/kg bw/day (250 mg/kg bw/day in the rat), based upon the body weight decrease at the top dose. In both rat and mouse it was demonstrated that imazaquin was devoid of carcinogenic potential. No genotoxic potential was demonstrated. In a three-generation study in the rat, there was no evidence of a treatment-related effect on mating, pregnancy or fertility indices, duration of gestation, litter size and survival, sex ratio or pup weights. The parental NOAEL was established at 5000 ppm (469 mg/kg bw/day). The reproductive and offspring NOAELs were set at ppm (corresponding to 917 mg/kg bw/day, highest dose tested). Imazaquin was not a developmental toxicant, in either the rat or the rabbit: in rats, both maternal and developmental NOAEL were 500 mg/kg bw/day; in the rabbit developmental toxicity study, maternal NOAEL was 250 mg/kg bw/day, based upon the presence of one fatality, and reduced body weight gain at the top dose. There was no evidence of treatment-related effects on the foetuses. The Acceptable Daily Intake (ADI) and the Acceptable Operator Exposure Level (AOEL) are both 0.25 mg/kg bw/day based on the NOAEL of the 1-year study in dogs, with a Safety Factor (SF) of 100. Based on the toxicity profile of imazaquin, an acute reference dose was not deemed necessary. The operator and worker exposure is below the AOEL (even without the use of personal protective equipment). The bystander exposure was also below the AOEL. The possible impact of each individual enantiomer toxicity on the risk assessment during re-entry activities does not represent a concern in view of the very low exposure values for workers consequent to the representative uses evaluated. 3. Residues It is noted that imazaquin is a mixture of enantiomers. The methods of analysis used in the residue studies were not stereoselective and the regulatory dossier provided no information on the behaviour of individual enantiomers. Therefore all residues reported in the residue section of this conclusion are for the sum of enantiomers. It is not known if either enantiomer is degraded more quickly than the other in the matrices studied. A study on spring wheat with imazaquin 14 C-labelled in the phenyl ring was submitted. It was representative for the notified cgap concerning growth stage and application rate. Whereas radioactive residues in grain were too low for identification of metabolites, imazaquin was found as the main compound in straw besides lower concentrations of CL , its methyl ester derivates and further unidentified metabolites. The plant residue definition for monitoring and for risk assessment for the representative use is imazaquin. 7

8 The magnitude of imazaquin residues was determined in a total of 16 field residue trials in winter wheat conducted in Northern and Southern European regions in three growing seasons. Field-testing parameters were consistent with the notified critical GAP. Imazaquin residues were below the LOQ (0.05 mg/kg) in all wheat grain and straw samples. Therefore the data set can be regarded as sufficient to propose an MRL for wheat grain at 0.05* mg/kg, despite the fact that only six trials carried out in Southern Europe have been submitted. As a plant growth regulator imazaquin interferes with plant growth and metabolism, and therefore the residue situation may differ from one cereal crop to the other. Hence, extrapolation to barley was not considered possible, and a data gap was identified for separate residue trials in barley. A freezer storage stability study in grain and straw indicated there was some degradation of the imazaquin residue level in grain. Therefore the issue of storage stability in grain should be considered when the new residue data for barley are generated. Studies on the effect of processing on the nature and level of residues were not required as residues in grain were below the LOQ. Based on a case made by the notifier it was concluded as unlikely that significant residues will occur in rotational crops, and thus a rotational crop study is not required to conclude the risk assessment for the representative uses of imazaquin. Exposure of livestock to residues of imazaquin is expected to be insignificant when cereal grain and straw after treatment with imazaquin is used as animal feed, as no residues above the LOQ were found in these matrices. Furthermore, imazaquin residues are not regarded as fat soluble and no bioaccumulation in tissues is expected. Therefore, metabolism studies on livestock or feeding studies are not required to conclude the risk assessment for the representative uses of imazaquin. A consumer risk assessment with the proposed MRL for wheat, using EFSA PRIMo rev. 2.0 indicated the chronic intake (TMDI) was less than 1 % of the ADI for all consumer groups. An acute risk assessment was not required since an ARfD was not set. With regard to the issue of isomers, for the representative uses the margin of safety for the consumer is deemed to be large considering the very low residues found for wheat (< LOQ) and expected for barley. 4. Environmental fate and behaviour As already discussed imazaquin and its metabolite CL contain a chiral carbon atom and so each consists of two enantiomers. These pairs of compounds were not quantified separately as the methods of analysis utilised in the studies did not differentiate the enantiomers. Reference to imazaquin and CL in the DAR and in this conclusion are therefore to the sum of the enantiomers, and the enantiomer ratio over time in the available experiments is unknown. In soil laboratory incubations under aerobic conditions in the dark, imazaquin exhibited moderate to high persistence, forming the major (>10 % applied radioactivity (AR)) metabolite CL (max % AR), which exhibited moderate persistence. Mineralisation of the phenyl ring radiolabel to carbon dioxide accounted for % AR after 122 days. The formation of unextractable residues (not extracted by acetonitrile followed by 0.5 N aqueous sodium hydroxide or just 0.5 N aqueous sodium hydroxide) for this radiolabel accounted for % AR after 122 days. In anaerobic soil incubations and under the conditions of a laboratory soil photolysis study (air dried soil) imazaquin was essentially stable. Imazaquin and CL exhibited very high mobility in soil. It was concluded that the adsorption of CL was not ph dependent. Whilst imazaquin would be expected to be more weakly adsorbed under neutral soil conditions than when soil was acidic or alkaline, overall, as imazaquin soil adsorption is low, it was accepted as appropriate to use the arithmetic mean adsorption value from the available soils in the environmental exposure assessment. In satisfactory field dissipation studies carried out at seven sites across Europe (spray application to the soil surface on bare soil plots in late spring), imazaquin exhibited a biphasic pattern of decline and low to moderate persistence. The levels of CL measured in the available field trials were not sufficient to estimate degradation rates for this metabolite under field conditions. 8

9 In laboratory incubations in dark aerobic natural sediment water systems, imazaquin exhibited very high persistence, forming no major metabolites (> 10 % AR). The unextractable sediment fraction (not extracted by 0.5 N aqueous sodium hydroxide) was a small sink for the phenyl ring 14 C- radiolabel, accounting for % AR at study end (100 days). Mineralisation of this radiolabel accounted for only % AR at the end of the study. In aqueous photolysis experiments imazaquin was readily transformed to six major degradation products: CL (max % AR), CL (max % AR), CL (max % AR), degradate B (max % AR), degradate E (max % AR) and degradate F (max % AR). Surface water and sediment exposure assessments (predicted environmental concentrations (PEC)) were carried out for imazaquin using the FOCUS step 1 and step 2 approach (version 1.1 of the Steps 1 2 in FOCUS calculator; FOCUS, 2001). Risk assessments for the six aqueous photodegradates and the major soil metabolite CL (that may runoff and drain to surface water systems) were completed using the available PEC for imazaquin. This approach was accepted in this case as: only simple Step 1 and Step 2 approaches had been followed; all these transformation products have lower molecular weights than imazaquin; and all the compounds would be expected to remain primarily in the water column of natural sediment water systems. The necessary groundwater exposure assessments were appropriately carried out using FOCUS (FOCUS, 2000) scenarios and the models PEARL and PELMO for the active substance imazaquin and the soil metabolite CL The potential for groundwater exposure from the representative uses by imazaquin and CL above the parametric drinking water limit of 0.1 µg/l was concluded to be low in geoclimatic situations that are represented by all nine FOCUS groundwater scenarios. The PEC in soil, surface water, sediment, and groundwater covering the representative uses assessed can be found in Appendix A of this conclusion. 5. Ecotoxicology The risk assessment was based on the following guidance documents: European Commission (2002a, 2002b, 2002c) and SETAC (2001). The risk of imazaquin to insectivorous and herbivorous birds via dietary exposure was assessed as low at tier 1 for the representative use in cereals. The acute and long-term risk to herbivorous and insectivorous mammals via dietary exposure was assessed as low at tier 1. An assessment of the risk to earthworm-eating birds and mammals was not required since log P ow < 3. Additionally, the risk to birds and mammals from consumption of contaminated water was assessed as low. Imazaquin is very toxic to aquatic organisms. The lowest endpoint driving the aquatic risk assessment was observed for Lemna gibba (EbC 50 = mg a.s./l). The risk of imazaquin to aquatic organisms was assessed as low at FOCUS sw Step 1 2 for the representative use in winter cereals. There were no aquatic organisms studies available for soil metabolite CL , therefore EFSA performed a standard risk assessment using the end-point for L. gibba EbC 50 divided by 10. The resulting endpoint of mg a.s./l gives TERs values of 4.6 and 21.5 for Steps 1 and 2 respectively, indicating a low risk. The risk assessments for the six aqueous photodegradates were completed using the available PEC for imazaquin, taking into account the percentage at which the metabolite was formed, and the lower 7 Simulations appropriately followed EFSA (2004) and utilised a Q10 of 2.2 and Walker equation coefficient of 0.7. The use of field degradation rates for parent imazaquin in simulations was in accordance with the principles of FOCUS (2006) kinetics and FOCUS (2000) groundwater guidance. 9

10 endpoint of imazaquin. Sufficiently large margins of safety were calculated for the soil metabolite CL and the six aqueous photodegradates, and therefore the risk was assessed as low. Whereas the off-field risk was assessed as low for the two standard test species Aphidius rhopalosiphi and Typhlodromus pyri, the in-field risk was assessed as high for A. rhopalosiphi and T. pyri for the representative use on cereals. The in-field risk was addressed based on two extended laboratory studies with A. rhopalosiphi and T. pyri. The adverse effects observed in the extended laboratory study were <, indicating a low risk for the non-target arthropods. The risk of imazaquin and the soil metabolite CL to earthworms was assessed as low. The risk to bees, non-target soil macro-organisms, non-target soil micro-organisms, non-target plants and the function of waste water treatment plants was assessed as low for the representative uses. No information was available on the preferential metabolism/degradation or ecotoxicology of each enantiomer of imazaquin or its transformation products, however margins between exposure and effect concentrations for all of the environmental risk assessments consequent to the representative uses were considered sufficient and no further information is needed for these uses. 10

11 6. Overview of the risk assessment of compounds listed in residue definitions triggering assessment of effects data for the environmental compartments 6.1. Soil Compound (name and/or code) Imazaquin CL Persistence Moderate to high persistence. Single first-order DT days (20ºC pf 2 soil moisture). Low to moderate persistence. European field dissipation studies biphasic kinetics DT days (DT days). Moderate persistence. Single first-order DT days (20ºC pf 2 soil moisture). Ecotoxicology The acute and long-term risk to earthworms was assessed as low. The lowest endpoint driving the risk assessment for earthworms is 56d reproduction NOEC = mg/kg dw soil (regulatory concentration including a safety factor of 5 = 0.2 mg/kg dw soil). The risk to soil micro-organisms and other soil macroorganisms was assessed as low. The risk to earthworms was assessed as low. 11

12 6.2. Ground water Compound (name and/or code) Mobility in soil >0.1 μg/l 1m depth for the representative uses (at least one FOCUS scenario or relevant lysimeter) Pesticidal activity Toxicological relevance Ecotoxicological activity Imazaquin Very high mobility. K Foc ml/g No Yes Yes Imazaquin is very toxic to aquatic organisms. Endpoint driving the aquatic risk assessment: aquatic plants EbC 50 = 31 µg a.s./l. The risk to aquatic organisms was assessed as low. CL Very high mobility. K Foc ml/g No No information available, not needed. No information available, not needed. No data available and not required. 12

13 6.3. Surface water and sediment Compound (name and/or code) Imazaquin CL (via runoff or drainage from soil) CL (formed by aqueous photolysis) CL (formed by aqueous photolysis) CL (formed by aqueous photolysis) Degradate B (formed by aqueous photolysis) Degradate E (formed by aqueous photolysis) Degradate F (formed by aqueous photolysis) Ecotoxicology Imazaquin is very toxic to aquatic organisms. Endpoint driving the aquatic risk assessment: aquatic plants EbC 50 = 31 µg a.s./l. A low risk to the aquatic environment was indicated in the surface water risk assessment. No data available and not required. The risk was assessed as low. The risk was assessed as low. The risk was assessed as low. The risk was assessed as low. The risk was assessed as low. The risk was assessed as low Air Compound (name and/or code) Imazaquin Toxicology Not acutely toxic via inhalation. 13

14 LIST OF STUDIES TO BE GENERATED, STILL ONGOING OR AVAILABLE BUT NOT PEER REVIEWED Imazaquin consists of two enantiomers. The preferential metabolism/degradation of each enantiomer of imazaquin and the transformation products that retain a chiral carbon in plants, animals and the environment, as well as the possible impact on the toxicity, the consumer risk assessment, worker exposure and the environment was not quantitatively assessed (relevant for all the representative uses assessed but not essential to conclude on the representative uses as the risk assessments have margins of safety, with the possible exception of the consumer risk assessment consequent from the use on winter barley; submission date proposed by the notifier unknown; see sections 2, 3, 4 and 5). Five batch data with analysis of hydrogen cyanide and toluene, together with a new specification (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 1). Notifier to confirm the formulation details (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 1). Confirmatory method of analysis for plants (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 1). Additional validation for the soil confirmatory method of analysis (recovery and RSD at different fortification levels) (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 1). Residue trials in barley. When conducting the trials attention should be paid to the issue of storage stability in grain, i.e. analysis immediately after harvest is recommended (relevant for the representative use in barley; submission date proposed by the notifier: unknown; see section 3). PARTICULAR CONDITIONS PROPOSED TO BE TAKEN INTO ACCOUNT TO MANAGE THE RISK(S) IDENTIFIED Imazaquin is not stable in the formulation and appropriate labelling should be considered to address this issue. ISSUES THAT COULD NOT BE FINALISED The consumer risk assessment for the use in barley. Residue data are not available for barley, and extrapolation from wheat data is not considered possible for plant growth regulators. CRITICAL AREAS OF CONCERN None. 14

15 REFERENCES Belgium, Draft Assessment Report (DAR) on the active substance imazaquin prepared by the rapporteur Member State Belgium in the framework of Directive 91/414/EEC, December Belgium, Final Addendum to Draft Assessment Report on imazaquin, compiled by EFSA, October EFSA (European Food Safety Authority), Opinion of the Scientific Panel on Plant Health, Plant Protection Products and their Residues on a request of EFSA related to FOCUS groundwater models comparability and the consistency of this risk assessment of groundwater contamination. The EFSA Journal (2004) 93, EFSA (European Food Safety Authority), Peer Review Report to the conclusion regarding the peer review of the pesticide risk assessment of the active substance imazaquin. European Commission, Review report for the active substance imazaquin Finalised in the Standing Committee on the Food Chain and Animal Health at its meeting on 14 March 2008 in view of the inclusion of imazaquin in Annex I of Directive 91/414/EEC. SANCO/832/08 rev. 2, 7 March FOCUS, FOCUS Groundwater Scenarios in the EU review of active substances. Report of the FOCUS Groundwater Scenarios Workgroup, EC Document Reference SANCO/321/2000- rev pp, as updated by the Generic Guidance for FOCUS groundwater scenarios, version 1.1 dated April 2002 FOCUS, FOCUS Surface Water Scenarios in the EU Evaluation Process under 91/414/EEC. Report of the FOCUS Working Group on Surface Water Scenarios, EC Document Reference SANCO/4802/2001-rev pp. FOCUS, Guidance Document on Estimating Persistence and Degradation Kinetics from Environmental Fate Studies on Pesticides in EU Registration Report of the FOCUS Work Group on Degradation Kinetics, EC Document Reference Sanco/10058/2005 version 2.0, 434 pp European Commission, 2002a. Guidance Document on Terrestrial Ecotoxicology Under Council Directive 91/414/EEC. SANCO/10329/2002 rev.2 final, 17 October European Commission, 2002b. Guidance Document on Aquatic Ecotoxicology Under Council Directive 91/414/EEC. SANCO/3268/2001 rev 4 (final), 17 October European Commission, 2002c. Guidance Document on Risk Assessment for Birds and Mammals Under Council Directive 91/414/EEC. SANCO/4145/2000. SETAC (Society of Environmental Toxicology and Chemistry), Guidance Document on Regulatory Testing and Risk Assessment procedures for Plant Protection Products with Non- Target Arthropods. ESCORT 2. 15

16 APPENDICES APPENDIX A LIST OF END POINTS FOR THE ACTIVE SUBSTANCE AND THE REPRESENTATIVE FORMULATION Identity, Physical and Chemical Properties, Details of Uses, Further Information Active substance (ISO Common Name) Function (e.g. fungicide) Imazaquin Plant growth regulator Rapporteur Member State Co-rapporteur Member State Belgium None Identity (Annex IIA, point 1) Chemical name (IUPAC) Chemical name (CA) CIPAC No 699 CAS No EC No (EINECS or ELINCS) FAO Specification (including year of publication) Minimum purity of the active substance as manufactured Identity of relevant impurities (of toxicological, ecotoxicological and/or environmental concern) in the active substance as manufactured 2-[(RS)-4-isopropyl-4-methyl-5-oxo-2-imidazolin-2- yl]quinoline-3-carboxylic acid (±)-2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo- 1H-imidazol-2-yl]-3-quinolinecarboxylic acid None Molecular formula C 17 H 17 N 3 O 3 No FAO specification at time of evaluation 960 g/kg (racemic mixture) hydrogen cyanide (HCN) max. content : OPEN; toluene max. content : OPEN Molecular mass Structural formula u COOH N N CH 3 HN CH(CH 3 ) 2 O 16

17 Physical and chemical properties (Annex IIA, point 2) Melting point (state purity) 220 to C (99.6%) Boiling point (state purity) Not applicable (decomposition occurs) Temperature of decomposition (state purity) 250 C (99.6%) Appearance (state purity) yellow-gray powdery fine-crystalline solid (99.6%); orange-gray powdery fine-crystalline solid (96.8%) Vapour pressure (state temperature, state purity) 7 x Pa at 20 C (99.6%) 2 x Pa at 25 C (99.6%) Henry s law constant 3.74 x Pa.m 3 /mol at 20 C Solubility in water (state temperature, state purity and ph) Solubility in organic solvents (state temperature, state purity) Surface tension (state concentration and temperature, state purity) Partition co-efficient (state temperature, ph and purity) 99.6% pure Milli-Q reagent water ph 5 buffer ph 7 buffer ph 9 buffer The water solubility is ph-dependent. 96.8% pure solubility at 20 C 58.3 mg/l 485 mg/l 102 g/l 345 g/l solubility at 20 C (g/l) hexane toluene 0.24 dichloromethane 14.5 methanol 5.77 acetone 3.69 ethyl acetate 1.49 acetonitrile 1.91 = 49.9 mn/m at 20 C (90% saturated aqueous solution) (96.8%) 99.6% pure Log Pow at 20 C buffer ph buffer ph buffer ph buffer ph buffer ph The partition coefficient is ph-dependent. Dissociation constant (state purity) pka 1 = 3.45 and pka II = at 20 C (99.6%) 17

18 UV/VIS absorption (max.) incl. (state purity, ph) 99.6% pure Sample solution Acidic * (0.1 M HCl; ph 1.01) Conc. test item [mol/l] waveleng th [nm] sh Absorbance [L/(mol.cm)] Neutral * (H 2 O; ph 6.57) sh Alkaline (0.1M NaOH; 1.39 x sh ph 12.76) sh = shoulder * = Dilution of saturated solution; molar concentration unknown and thus, molar absorption coefficient cannot be calculated Flammability (state purity) Not highly flammable (96.8%) Not auto-flammable (96.8%) Explosive properties (state purity) Not explosive (96.8%) Oxidising properties (state purity) Not oxidising (96.8%)

19 Summary of representative uses evaluated (imazaquin)* Pests or Member F Group of Crop and/ State Product G pests or situation or name or controlled Country I Formulation Application Application rate per treatment PHI (days) Remar ks (a) (b ) (c) Type (d-f) Conc of as (i) method kind (f-h) growth stage & season (j) number min max (k) interval between applications (min) g as/hl min max water L/ha min max g as/ha min max (l) (m) Winter wheat EU Meteor (BAS W) F Plant growth regulator (prevents lodging) SL 0.8 g/l (1) Tractor mounted spray Leaf sheath lengthening to 1 st node detectable 1 NA Not relevant (2) (BBCH 30-32) Winter barley EU Meteor (BAS W) F Plant growth regulator (prevents lodging) SL 0.8 g/l (1) Tractor mounted spray Leaf sheath lengthening to 1st node detectable 1 NA Not relevant (2) [I] (BBCH 30-32) g/l of imazaquin and 368 g/l chlormequat chloride. 2 Last growth stage for application before BBCH 32. [I] consumer risk assessment not finalised due to a data gap, i.e. the necessary residue trials were not available. For uses where the column "Remarks" is marked in grey further consideration is necessary. Uses should be crossed out when the notifier no longer supports this use(s). (a) For crops, the EU and Codex classifications (both) should be taken into account; where relevant, the use situation should be described (e.g. fumigation of a structure) (b) Outdoor or field use (F), greenhouse application (G) or indoor application (I) (c) e.g. biting and suckling insects, soil born insects, foliar fungi, weeds (d) e.g. wettable powder (WP), emulsifiable concentrate (EC), granule (GR) (e) GCPF Codes - GIFAP Technical Monograph No 2, 1989 (f) All abbreviations used must be explained (g) Method, e.g. high volume spraying, low volume spraying, spreading, dusting, drench (h) Kind, e.g. overall, broadcast, aerial spraying, row, individual plant, between the plant- type of equipment used must be indicated(i) g/kg or g/l. (j) Growth stage at last treatment (BBCH Monograph, Growth Stages of Plants, 1997, Blackwell, ISBN ), including where relevant, information on season at time of application (k) Indicate the minimum and maximum number of application possible under practical conditions of use (l) The values should be given in g or kg whatever gives the more manageable number (e.g. 200 kg/ha instead of g/ha or 12.5 g/ha instead of kg/ha (m) PHI - minimum pre-harvest interval 19

20 Methods of Analysis Analytical methods for the active substance (Annex IIA, point 4.1) Technical as (analytical technique) Impurities in technical as (analytical technique) Plant protection product (analytical technique) HPLC-UV HPLC-UV, Karl-Fischer, gravimetric analysis HPLC-UV Analytical methods for residues (Annex IIA, point 4.2) Residue definitions for monitoring purposes Food of plant origin Imazaquin Food of animal origin not required Soil Imazaquin Water surface Imazaquin drinking/ground Imazaquin Air Imazaquin Monitoring/Enforcement methods Food/feed of plant origin (analytical technique and LOQ for methods for monitoring purposes) Food/feed of animal origin (analytical technique and LOQ for methods for monitoring purposes) HPLC-UV, LOQ = 0.05 mg/kg (imazaquin) (wheat grain, wheat straw, wheat whole material), ILV available Confirmatory method: OPEN Not required, as no MRLs are proposed Soil (analytical technique and LOQ) LC-MS, LOQ = 1 µg/kg (imazaquin; CL ) Water (analytical technique and LOQ) Confirmatory method: OPEN LC-MS (conf. by LC-MS/MS), LOQ = 0.1 µg/l (imazaquin) Air (analytical technique and LOQ) LC-MS (conf. by LC-MS/MS), LOQ = 7.5 µg/m 3 Body fluids and tissues (analytical technique and LOQ) (imazaquin) Not required, since imazaquin is not considered to be toxic or very toxic Classification and proposed labelling with regard to physical and chemical data (Annex IIA, point 10) RMS/peer review proposal Active substance none 20

21 Absorption, distribution, excretion and metabolism in mammals (Annex IIA, point 5.1) Rate and extent of oral absorption Distribution Potential for accumulation Rapid (<24h) and completely (84-94%) absorbed Low, as <0.1% of the dose was recovered in tissues or carcass None Rate and extent of excretion Rapidly (<24h) and completely excreted, via urine (82-89%) and faeces (2-4%) Metabolism in animals No evidence of metabolisation in the rat Toxicologically relevant compounds (animals and plants) Toxicologically relevant compounds (environment) Imazaquin Imazaquin Acute toxicity (Annex IIA, point 5.2) Rat LD 50 oral > 5000 mg/kg bw - Mouse LD 50 oral 1752 mg/kg bw R22 Rabbit LD 50 dermal > 5000 mg/kg bw - Rat LC 50 inhalation >5.7 mg/l/4 h (whole body) - Skin irritation Non-irritant - Eye irritation Non-irritant - Skin sensitisation Non-sensitiser (M & K) - Short term toxicity (Annex IIA, point 5.3) Target / critical effect Relevant oral NOAEL Relevant dermal NOEL Relevant inhalation NOAEL Dog: skeletal myopathy, anaemia, and related haematological and clinico-chemical alterations (increased creatinine phosphokinase, lactate dehydrogenase, transaminases activity and total bilirubin levels) Rat: no effects up to the highest dose tested of 800 mg/kg bw/day 1-year dog: 25 mg/kg bw/day 90-day rat: 800 mg/kg bw/day 21d, rat: 500 mg/kg bw/day No data not required Genotoxicity (Annex IIA, point 5.4) Not genotoxic 21

22 Long term toxicity and carcinogenicity (Annex IIA, point 5.5) Target/critical effect Relevant NOAEL Carcinogenicity Reduced bodyweight (gain) 2 year rat: 250 mg/kg bw/day 2 year mouse: 150 mg/kg bw/day No carcinogenic potential Reproductive toxicity (Annex IIA, point 5.6) Multigeneration study Reproduction target / critical effect Relevant parental NOAEL Relevant reproductive NOAEL Relevant offspring NOAEL Parental: kidney pelvis calcification ( ) 469 mg/kg bw/day 917 mg/kg bw/day (highest dose tested) 917 mg/kg bw/day (highest dose tested) Developmental toxicity Developmental target / critical effect Relevant maternal NOAEL Relevant developmental NOAEL Developmental toxicity (in rabbit reduced pup weight and reduced ossification in rats) at maternally toxic doses (mortality, clinical signs) No teratogenic effects. Rat: 500 mg/kg bw/day Rabbit: 250 mg/kg bw/day Rat and rabbit: 500 mg/kg bw/day Neurotoxicity (Annex IIA, point 5.7) Acute neurotoxicity Repeated neurotoxicity Delayed neurotoxicity No data not required. No data not required. No data not required. Other toxicological studies (Annex IIA, point 5.8) Mechanistic studies Studies performed on metabolites None None Medical data (Annex IIA, point 5.9) No evidence of toxicological concern from medical surveillance of manufacturing plant personnel. No cases of poisoning. Summary (Annex IIA, point 5.10) Value Study Safety factor ADI 0.25 mg/kg bw/day 1-year dog study 100 AOEL 0.25 mg/kg bw/day 1-year dog study 100 ARfD (acute reference dose) Not allocated not necessary 22

23 Dermal absorption (Annex IIIA, point 7.3) No study, default value 100% (concentrate and dilution) Acceptable exposure scenarios (including method of calculation) Operator Application in cereals UK-POEM % of AOEL (tractor boom sprayer, kg a.s./ha, without PPE) 9.7% BBA (tractor boom sprayer, kg a.s./ha, without PPE) 1.0% Workers According to Hoernicke, 1998 and using EUROPOEM dislodgeable foliar residue and transfer coefficient values : 0.2 % of AOEL (no PPE) Bystanders According to Lloyd and Bell, 1983: 0.024% of AOEL Classification and proposed labelling (Annex IIA, point 10) with regard to toxicological data Xn ; R22 ( Harmful if swallowed ) 23

24 Metabolism in plants (Annex IIA, point 6.1 and 6.7, Annex IIIA, point 8.1 and 8.6) Plant groups covered Rotational crops Metabolism in rotational crops similar to metabolism in primary crops? Processed commodities Residue pattern in processed commodities similar to residue pattern in raw commodities? Plant residue definition for monitoring Plant residue definition for risk assessment Conversion factor (monitoring to risk assessment) Cereals (Spring wheat) A case was made that investigation of rotational crop residues is not required for the representative uses. Not applicable Processing studies not required Not applicable Imazaquin Imazaquin Not applicable Metabolism in livestock (Annex IIA, point 6.2 and 6.7, Annex IIIA, point 8.1 and 8.6) Animals covered Time needed to reach a plateau concentration in milk and eggs Animal residue definition for monitoring Animal residue definition for risk assessment Conversion factor (monitoring to risk assessment) Metabolism in rat and ruminant similar (yes/no) Fat soluble residue: (yes/no) Lactating goats and Laying hens -Milk: Total residues below the detection limit of the radio assay method (0.01 mg/kg). -Eggs: total residues plateaued at day-3 (max. residue concentration of mg/kg). Not required. Not required. Not applicable Yes no Residues in succeeding crops (Annex IIA, point 6.6, Annex IIIA, point 8.5) No soil accumulation of Imazaquin residues is expected. A case was made that investigation of rotational crop residues is not required for the representative uses. Stability of residues (Annex IIA, point 6 introduction, Annex IIIA, point 8 Introduction) A significant degradation of the residue levels of Imazaquin in wheat grain (33 %) was observed within 174 days of the frozen storage at 18 C and reached 40 % of degradation of the level during the course of the frozen storage period. Residues of Imazaquin in wheat straw can be considered as stable under frozen storage conditions for a period of around 24 months. 24

25 Residues from livestock feeding studies (Annex IIA, point 6.4, Annex IIIA, point 8.3) Ruminant: Poultry: Pig: Conditions of requirement of feeding studies Expected intakes by livestock 0.1 mg/kg diet (dry weight basis) (yes/no - If yes, specify the level) No No No Potential for accumulation (yes/no): No No No Metabolism studies indicate potential level of residues 0.01 mg/kg in edible tissues (yes/no) No No No Feeding studies (Specify the feeding rate in cattle and poultry studies considered as relevant) Not required. Residue levels in matrices: Mean (max) mg/kg Muscle Liver Kidney Fat Milk - Eggs - 25

26 Summary of residues data according to the representative uses on raw agricultural commodities and feedingstuffs (Annex IIA, point 6.3, Annex IIIA, point 8.2) Crop Northern or Mediterranean Region, field or glasshouse, and any other useful information Trials results relevant to the representative uses (a) Recommendation/comments MRL estimated from trials according to the representative use HR (c) STMR (b) Northern EU -Wheat grain: 10x < 0.05 mg/kg -Wheat straw: 10x < 0.05 mg/kg Trials characterized by one application at a dose rate of kg a.s./ha, spray concentration of kg a.s./hl, L/ha, at a growth stage BBCH and at BBCH <0.05 mg/kg <0.05 mg/kg Winter wheat Southern EU -Wheat grain: 6x < 0.05 mg/kg -Wheat straw: 6x < 0.05 mg/kg Trials characterized by one application at a dose rate of application of kg a.s./ha, spray concentration of kg a.s./hl, L/ha at a growth stage BBCH * mg/kg <0.05 mg/kg <0.05 mg/kg Winter barley Northern EU Southern EU Additional residue trials are required on barley (data gap). Extrapolation from wheat not considered possible for uses of Plant growth regulators (PRAPeR 30). (a) Numbers of trials in which particular residue levels were reported e.g. 3 x <0.01, 1 x 0.01, 6 x 0.02, 1 x 0.04, 1 x 0.08, 2 x 0.1, 2 x 0.15, 1 x 0.17 (b) Supervised Trials Median Residue i.e. the median residue level estimated on the basis of supervised trials relating to the representative use (c) Highest residue open open open 26

27 Consumer risk assessment (Annex IIA, point 6.9, Annex IIIA, point 8.8) ADI TMDI (% ADI) WHO according to EFSA PRIMo rev.2a TMDI (% ADI) according to national (to be specified) diets IEDI (WHO European Diet) (% ADI) NEDI (specify diet) (% ADI) Factors included in IEDI and NEDI ARfD IESTI (% ARfD) NESTI (% ARfD) according to national (to be specified) large portion consumption data Factors included in IESTI and NESTI 0.25 mg/kg bw/day <1% (0.2 % WHO cluster diet B) UK 10 consumer categories: <1.0% German children, 2-5 years: 0.08 % Not required Not required Not applicable Not allocated Not applicable Not applicable Not applicable Processing factors (Annex IIA, point 6.5, Annex IIIA, point 8.4) Crop/ process/ processed product Number of studies Processing factors Amount Transfer factor Yield factor transferred (%) (Optional) Cereals N/a: not applicable No studies required, residues <0.1 mg/kg Proposed MRLs (Annex IIA, point 6.7, Annex IIIA, point 8.6) n/a n/a n/a Wheat grain Barley grain 0.05* mg/kg Open (data gap for residue trials) 27

28 Route of degradation (aerobic) in soil (Annex IIA, point ) Mineralization after 100 days % after 4 months, [ 14 C-phenyl]-label (5 soils) Non-extractable residues after 100 days % after 4 months, [ 14 C-phenyl]-label (5 soils) Metabolites requiring further consideration - name and/or code, % of applied (range and maximum) 2-(RS-{[1-(aminocarbonyl)-1,2- dimethylpropyl]amino}carbonyl)-3-quinolinecarboxylic acid.(cl ) maxima of 1.6 to 5.4 % AR (5 soils) at 4 months % AR at 4 months to a year. Route of degradation in soil - Supplemental studies (Annex IIA, point ) Anaerobic degradation Mineralization after 100 days Non-extractable residues after 100 days Metabolites that may require further consideration for risk assessment - name and/or code, % of applied (range and maximum) Soil photolysis Metabolites that may require further consideration for risk assessment - name and/or code, % of applied (range and maximum) Not required essentially stable under anaerobic conditions Not required essentially stable under anaerobic conditions Not required essentially stable under anaerobic conditions essentially stable under the conditions of a laboratory soil photolysis study 28