FAO SPECIFICATIONS AND EVALUATIONS FOR AGRICULTURAL PESTICIDES

IMIDACLOPRID

1-(6-Chloro-3-pyridinylmethyl)-N-nitroimidazolidin-2ylideneamine

TABLE OF CONTENTS IMIDACLOPRID

Page DISCLAIMER INTRODUCTION PART ONE SPECIFICATIONS FOR IMIDACLOPRID IMIDACLOPRID INFORMATION IMIDACLOPRID TECHNICAL MATERIAL (APRIL 2006) IMIDACLOPRID GRANULES (APRIL 2006 and JUNE 2008) IMIDACLOPRID WATER DISPERSIBLE POWDER FOR SLURRY SEED TREATMENT (APRIL 2006) IMIDACLOPRID WATER DISPERSIBLE GRANULES (APRIL 2006) IMIDACLOPRID AQUEOUS SUSPENSION CONCENTRATE (APRIL 2006) IMIDACLOPRID SUSPENSION CONCENTRATE FOR SEED TREATMENT (APRIL 2006) IMIDACLOPRID OIL-BASED SUSPENSION CONCENTRATE (APRIL 2006) IMIDACLOPRID SOLUBLE CONCENTRATE (APRIL 2006) 2 3 4 5 7 9 11 14 16 19 1

PART TWO EVALUATIONS OF IMIDACLOPRID 2004 FAO/WHO EVALUATION REPORT ON IMIDACLOPRID SUPPORTING INFORMATION ANNEX 1: HAZARD SUMMARY PROVIDED BY THE PROPOSER ANNEX 2: REFERENCES 2008 ADDENDUM REPORT 21 22 24 29 33 36

DISCLAIMER1

FAO specifications are developed with the basic objective of promoting, as far as practicable, the manufacture, distribution and use of pesticides that meet basic quality requirements. Compliance with the specifications does not constitute an endorsement or warranty of the fitness of a particular pesticide for a particular purpose, including its suitability for the control of any given pest, or its suitability for use in a particular area. Owing to the complexity of the problems involved, the suitability of pesticides for a particular purpose and the content of the labelling instructions must be decided at the national or provincial level. Furthermore, pesticides which are manufactured to comply with these specifications are not exempted from any safety regulation or other legal or administrative provision applicable to their manufacture, sale, transportation, storage, handling, preparation and/or use. FAO disclaims any and all liability for any injury, death, loss, damage or other prejudice of any kind that may arise as a result of, or in connection with, the manufacture, sale, transportation, storage, handling, preparation and/or use of pesticides which are found, or are claimed, to have been manufactured to comply with these specifications. Additionally, FAO wishes to alert users to the fact that improper storage, handling, preparation and/or use of pesticides can result in either a lowering or complete loss of safety and/or efficacy. FAO is not responsible, and does not accept any liability, for the testing of pesticides for compliance with the specifications, nor for any methods recommended and/or used for testing compliance. As a result, FAO does not in any way warrant or represent that any pesticide claimed to comply with a FAO specification actually does so.

This disclaimer applies to all specifications published by FAO.

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INTRODUCTION FAO establishes and publishes specifications* for technical material and related formulations of agricultural pesticides, with the objective that these specifications may be used to provide an international point of reference against which products can be judged either for regulatory purposes or in commercial dealings. Since 1999 the development of FAO specifications follows the New Procedure, described in the 5th edition of the Manual on the development and use of FAO specifications for plant protection products (FAO Plant Production and Protection Page No. 149). This New Procedure follows a formal and transparent evaluation process. It describes the minimum data package, the procedure and evaluation applied by FAO and the Experts of the FAO/WHO Joint Meeting on Pesticide Specifications (JMPS). [Note: prior to 2002, the Experts were of the FAO Panel of Experts on Pesticide Specifications, Registration Requirements, Application Standards and Prior Informed Consent, which now forms part of the JMPS, rather than the JMPS.] FAO Specifications now only apply to products for which the technical materials have been evaluated. Consequently from the year 2000 onwards the publication of FAO specifications under the New Procedure has changed. Every specification consists now of two parts namely the specifications and the evaluation report(s): PART ONE: The Specification of the technical material and the related formulations of the plant protection product in accordance with chapter 4, 5 and 6 of the 5th edition of the Manual on the development and use of FAO specifications for plant protection products. PART TWO: The Evaluation Report(s) of the plant protection product reflecting the evaluation of the data package carried out by FAO and the JMPS. The data are to be provided by the manufacturer(s) according to the requirements of Appendix A, annex 1 or 2 of the Manual on the development and use of FAO specifications for plant protection products and supported by other information sources. The Evaluation Report includes the name(s) of the manufacturer(s) whose technical material has been evaluated. Evaluation reports on specifications developed subsequently to the original set of specifications are added in a chronological order to this report. FAO specifications under the New Procedure do not necessarily apply to nominally similar products of other manufacturer(s), nor to those where the active ingredient is produced by other routes of manufacture. FAO has the possibility to extend the scope of the specifications to similar products but only when the JMPS has been satisfied that the additional products are equivalent to that which formed the basis of the reference specification. Specifications bear the date (month and year) of publication of the current version. Dates of publication of the earlier versions, if any, are identified in a footnote. Evaluations bear the date (year) of the meeting at which the recommendations were made by the JMPS. * NOTE: PUBLICATIONS ARE AVAILABLE ON THE INTERNET AT (http://www.fao.org/ag/agp/agpp/pesticid/)
OR IN HARDCOPY FROM THE PLANT PROTECTION INFORMATION OFFICER.

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PART ONE SPECIFICATIONS

IMIDACLOPRID Page IMIDACLOPRID INFORMATION IMIDACLOPRID TECHNICAL MATERIAL (APRIL 2006) IMIDACLOPRID GRANULES (APRIL 2006 and JUNE 2008) IMIDACLOPRID WATER DISPERSIBLE POWDER FOR SLURRY SEED TREATMENT (APRIL 2006) IMIDACLOPRID WATER DISPERSIBLE GRANULES (APRIL 2006) IMIDACLOPRID AQUEOUS SUSPENSION CONCENTRATE (APRIL 2006) IMIDACLOPRID SUSPENSION CONCENTRATE FOR SEED TREATMENT (APRIL 2006) IMIDACLOPRID OIL-BASED SUSPENSION CONCENTRATE (APRIL 2006) IMIDACLOPRID SOLUBLE CONCENTRATE (APRIL 2006) 3 4 5 7 9 11 14 16 19

FAO SPECIFICATIONS AND EVALUATIONS FOR IMIDACLOPRID Page 3 of 38

IMIDACLOPRID INFORMATION ISO common names Imidacloprid (BSI, E-ISO), imidaclopride ((m) draft F-ISO) Synonyms BAY NTN 33 893 Chemical names IUPAC 1-(6-chloro-3-pyridinylmethyl)-N-nitroimidazolidin-2-ylideneamine CA 1-[(6-chloro-3-pyridinyl)methyl]-N-nitro-2-imidazolidinimine
NO2

Structural formula
N N NH Cl N

Empirical formula C9H10ClN5O2 Relative molecular mass 255.7 CAS Registry number 138261-41-3 CIPAC number 582 Identity tests HPLC retention time, IR and 1H-NMR spectra.

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IMIDACLOPRID TECHNICAL MATERIAL FAO specification 582/TC (April 2006)

This specification, which is PART ONE of this publication, is based on an evaluation of data submitted by the manufacturer whose name is listed in the evaluation report (582/2004). It should be applicable to relevant products of these manufacturers but it is not an endorsement of those products, nor a guarantee that they comply with the specifications. The specification may not be appropriate for the products of other manufacturers. The evaluation report (582/2004) as PART TWO forms an integral part of this publication.

1 Description The material shall consist of imidacloprid together with related manufacturing impurities and shall be a beige powder, free from visible extraneous matter and added modifying agents. 2 Active ingredient 2.1 Identity tests (582/TC/M/2, CIPAC Handbook K, p.70, 2003) The active ingredient shall comply with an identity test and, where the identity remains in doubt, shall comply with at least one additional test. 2.2 Imidacloprid content (582/TC/M/3, CIPAC Handbook K, p.70, 2003) The imidacloprid content shall be declared (not less than 970 g/kg) and, when determined, the average measured content shall not be lower than the declared minimum content.

Specifications may be revised and/or additional evaluations may be undertaken. Ensure the use of current versions by checking at: http://www.fao.org/ag/agp/agpp/pesticid/.

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IMIDACLOPRID GRANULES FAO specification 582/GR (May 2006 and June 2008)
This specification, which is PART ONE of this publication, is based on an evaluation of data submitted by the manufacturers whose names are listed in the evaluation reports (582/2004 and 582/2008). It should be applicable to relevant products of these manufacturers but it is not an endorsement of those products, nor a guarantee that they comply with the specifications. The specification may not be appropriate for the products of other manufacturers. The evaluation report (582/2004) as PART TWO forms an integral part of this publication. The evaluation report (582/2008) as an addendum to PART TWO forms an integral part of this publication

1 Description
The material shall consist of granules containing technical imidacloprid, complying with the requirements of FAO specification 582/TC (MAY 2006) together with suitable carriers and any other necessary formulants, in the form of rounded beige or colored granules. It shall be dry, free from visible extraneous matter and hard lumps, freeflowing, nearly dust free and intended for application by machine.

2 Active ingredient 2.1 Identity tests (582/GR/M/2, CIPAC Handbook H, p.190, 1998) The active ingredient shall comply with an identity test and, where the identity remains in doubt, shall comply with at least one additional test. 2.2 Imidacloprid content (582/GR/M/3, CIPAC Handbook, p.190, 1998) The imidacloprid content shall be declared (g/kg) and, when determined, the average measured content shall not differ from that declared by more than the following tolerances: Declared content, g/kg up to 25 above 25 up to 100 Note: the upper limit is included in the range 3 Relevant impurities 3.1 Water (MT 30.5, CIPAC Handbook J, p.120, 2000) Maximum: 1 g/kg. 4. Physical properties 4.1 Pour and tap density (MT 186, CIPAC Handbook K, p.151, 2003) Pour density: 1.4 to 1.6 g/ml.
Specifications may be revised and/or additional evaluations may be undertaken. Ensure the use of current versions by checking at: http://www.fao.org/ag/agp/agpp/pesticid/.

Tolerance 25% of the declared content 10% of the declared content

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Tap density: 1.5 to 1.7 g/ml. 4.2 Nominal size range (MT 58, CIPAC Handbook F, p.173, 1995) Not less than 950 g/kg of the formulation shall be within the size range 300 to 900 m. 4.3 Dustiness (MT 171, CIPAC Handbook F, p.425, 1995) Nearly dust free (Note 1). 4.4 Attrition resistance (MT178, CIPAC Handbook H, p.304, 1998) Minimum: 99% attrition resistance. 5 Storage stability 5.1 Stability at elevated temperature (MT 46.3, CIPAC Handbook J, p.128, 2000) After storage at 54 2 for 14 days, the determined average active ingredient C content must not be lower than 95% relative to the determined average content found before storage (Note 2) and the formulation shall continue to comply with the clauses for: nominal size range (4.2); dustiness (4.3) attrition resistance (4.4). -----------------------------------------------------------------------------------------------------------Note 1 The optical method, MT 171, usually shows good correlation with the gravimetric method and can, therefore, be used as an alternative where the equipment is available. Where the correlation is in doubt, it must be checked with the formulation to be tested. In case of dispute the gravimetric method shall be used. Note 2 Samples of the formulation taken before and after the storage stability test should be analyzed concurrently after the test in order to reduce the analytical error.

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IMIDACLOPRID WATER DISPERSIBLE POWDER FOR SLURRY SEED TREATMENT FAO specification 582/WS (April 2006)
This specification, which is PART ONE of this publication, is based on an evaluation of data submitted by the manufacturer whose name is listed in the evaluation report (582/2004). It should be applicable to relevant products of these manufacturers but it is not an endorsement of those products, nor a guarantee that they comply with the specifications. The specification may not be appropriate for the products of other manufacturers. The evaluation report (582/2004) as PART TWO forms an integral part of this publication.

1 Description The material shall consist of an homogeneous mixture of technical imidacloprid, complying with the requirements of FAO specification 582/TC (April 2006), together with carriers and any other necessary formulants, including colouring matter (Note 1). It shall be in the form of a fine powder, free from visible extraneous matter and hard lumps. 2 Active ingredient 2.1 Identity tests (CIPAC 582/WS/M2, CIPAC Handbook K, p.70, 2003) The active ingredient shall comply with an identity test and, where the identity remains in doubt, shall comply with at least one additional test. 2.2 Imidacloprid content (CIPAC 582/WS/M3, CIPAC Handbook K, p.70, 2003) The imidacloprid content shall be declared (g/kg) and, when determined, the content measured shall not differ from that declared by more than the following tolerances.
Declared content, g/kg above 250 up to 500 above 500 Note: the upper limit is included in the lower range Tolerance 5% of the declared content 25 g/kg

3 Relevant impurities 3.1 Water (MT 30.5, CIPAC Handbook J, p.120, 2000) Maximum: 20 g/kg.

Specifications may be revised and/or additional evaluations may be undertaken. Ensure the use of current versions by checking at: http://www.fao.org/ag/agp/agpp/pesticid/.

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4 Physical properties 4.1 Wet sieve test (MT 185, CIPAC Handbook K, p.148, 2003) (Note 2) Maximum: 0.1% of the formulation shall be retained on a 75 m test sieve. 4.2 Persistent foam (MT 47.2, CIPAC Handbook F, p.152, 1995) (Note 3) Maximum: 20 ml after 1 min. 4.3 Wettability (MT 53.3, CIPAC Handbook F, p.165, 1995) The formulation shall be completely wetted in 1 min without swirling. 5 Storage stability 5.1 Stability at elevated temperature (MT 46.3, CIPAC Handbook J, p.128, 2000) After storage at 54 2 for 14 days the determined average active C ingredient content must not be lower than 95% relative to the determined average content found before storage (Note 4) and the formulation shall continue to comply with the clause for: wet sieve test (4.1).
Note 1 The formulation shall contain a dye or pigment that permanently colours the seed after treatment (red is recommended) and cannot be removed by washing with water. In some countries, there may be a legal requirement that a specific colour shall be used. The same colour must not be used for denaturing seeds to be used as livestock feeding stuffs. This test should be performed at the application concentration. The mass of sample to be used in the test should be specified at the highest rate of use recommended by the supplier. Samples of the formulation taken before and after the storage stability test should be analyzed concurrently after the test in order to reduce the analytical error.

Note 2 Note 3 Note 4

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IMIDACLOPRID WATER DISPERSIBLE GRANULES FAO specification 582/WG (April 2006)

This specification, which is PART ONE of this publication, is based on an evaluation of data submitted by the manufacturer whose name is listed in the evaluation report (582/2004). It should be applicable to relevant products of these manufacturers but it is not an endorsement of those products, nor a guarantee that they comply with the specifications. The specification may not be appropriate for the products of other manufacturers. The evaluation report (582/2004) as PART TWO forms an integral part of this publication.

1 Description The material shall consist of an homogeneous mixture of technical imidacloprid, complying with the requirements of the FAO specification 582/TC (April 2006), together with carriers and any other necessary formulants. It shall be in the form of spherical granules, with a nominal size range of 0.1 to 0.8 mm and an average of approximately 0.4 to 0.5 mm, for application after disintegration and dispersion in water. The formulation shall be dry, free-flowing, essentially non-dusty, and free from visible extraneous matter and hard lumps. 2 Active ingredient 2.1 Identity tests (CIPAC 582/WG/M2, CIPAC Handbook K, p.70, 2003) The active ingredient shall comply with an identity test and, where the identity remains in doubt, shall comply with at least one additional test. 2.2 Imidacloprid content (CIPAC 582/WG/M3, CIPAC Handbook K, p.70, 2003) The imidacloprid content shall be declared (g/kg) and, when determined, the content measured shall not differ from that declared by more than the following tolerance.
Declared content, g/kg above 500 Tolerance 25 g/kg

3 Physical properties 3.1 Wettability (MT 53.3, CIPAC Handbook F, p.165, 1995) The formulation shall be completely wetted in 5 seconds, without swirling. 3.2 Wet sieve test (MT 185, CIPAC Handbook K, p.148, 2003) Maximum: 0.1% retained on a 75 m test sieve.

Specifications may be revised and/or additional evaluations may be undertaken. Ensure the use of current versions by checking at: http://www.fao.org/ag/agp/agpp/pesticid/.

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3.3 Degree of dispersion (MT 174, CIPAC Handbook F, p.435, 1995) Dispersibility: minimum 80% after 1 minute of stirring. 3.4 Suspensibility (MT 184, CIPAC Handbook K, p.142, 2003) (Notes 1 & 2) A minimum of 95% after 10 min and a minimum of 90% after 30min shall be in suspension in CIPAC standard water D at 30 2 C. 3.5 Persistent foam (MT 47.2, CIPAC Handbook F, p.152, 1995) (Note 3) Maximum: 20 ml after 1 minute. 3.6 Dustiness (MT 171, CIPAC Handbook F, p.425, 1995) (Note 4) Nearly dust free. 3.7 Flowability (MT 172, CIPAC Handbook F, p.430, 1995) At least 95 % of the formulation shall pass through a 5 mm test sieve after 20 drops of the sieve. 4 Storage stability 4.1 Stability at elevated temperature (MT 46.3, CIPAC Handbook J, p.128, 2000) After storage at 54 2C for 14 days, the determined average active ingredient content must not be lower that 97%, relative to the determined average content found before storage (Note 5) and the formulation shall continue to comply with the clauses for: wet sieve test (3.2); degree of dispersion (3.3); suspensibility (3.4); dustiness (3.6) flowability (3.7).
Note 1 Note 2 The formulation should be tested at the highest and lowest rates of use recommended by the supplier. Chemical assay is the only fully reliable method to measure the mass of active ingredient still in suspension. However, the simpler gravimetric method, MT 168, may be used on a routine basis provided that it has been shown to give equal results to those of chemical assay. In case of dispute, chemical assay shall be the "referee method". The mass of sample to be used in the test should be specified at the highest rate recommended by the supplier. Measurement of dustiness must be carried out on the sample "as received" and, where practicable, the sample should be taken from a newly opened container, because changes in the water content of samples may influence dustiness significantly. The optical method, MT 171, usually shows good correlation with the gravimetric method and can, therefore, be used as an alternative where the equipment is available. Where the correlation is in doubt, it must be checked with the formulation to be tested. In case of dispute the gravimetric method shall be used. Analysis of the formulation, before and after the storage stability test, should be carried out concurrently (i.e. after storage) to reduce analytical error.

Note 3 Note 4

Note 5

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IMIDACLOPRID AQUEOUS SUSPENSION CONCENTRATE FAO specification 582/SC (April 2006)

This specification, which is PART ONE of this publication, is based on an evaluation of data submitted by the manufacturer whose name is listed in the evaluation report (582/2004). It should be applicable to relevant products of these manufacturers but it is not an endorsement of those products, nor a guarantee that they comply with the specifications. The specification may not be appropriate for the products of other manufacturers. The evaluation report (582/2004) as PART TWO forms an integral part of this publication.

1 Description The material shall consist of a whitish suspension of fine particles of technical imidacloprid, complying with the requirements of FAO specification 582/TC (April 2006), in an aqueous phase together with suitable formulants. After gentle agitation the material shall be homogeneous (Note 1) and suitable for further dilution in water. 2 Active ingredient 2.1 Identity tests (582/SC/M/2, CIPAC Handbook K, p.70, 2003) The active ingredient shall comply with an identity test and, where the identity remains in doubt, shall comply with at least one additional test. 2.2 Imidacloprid content (582/SC/M/3, CIPAC Handbook K, p.70, 2003) The imidacloprid content shall be declared (g/kg or g/l at 20 2C, Note 2) and, when determined, the average measured content shall not differ from that declared by more than the following tolerances:
Declared content, g/kg or g/l at 20 2C up to 25 above 25 up to 100 above 100 up to 250 above 250 up to 500 Note: the upper limit is included in each range Tolerance 15% of the declared content 10% of the declared content 6% of the declared content 5% of the declared content

3 Physical properties 3.1 Pourability (MT 148.1, CIPAC Handbook F, p.348, 1995) Maximum "residue": 4%.

Specifications may be revised and/or additional evaluations may be undertaken. Ensure the use of current versions by checking at: http://www.fao.org/ag/agp/agpp/pesticid/.

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3.2 Spontaneity of dispersion (MT 160, CIPAC Handbook F, p.391, 1995) (Note 3) A minimum of 90% of the imidacloprid content found under 2.2 shall be in suspension after 5 minutes in CIPAC Standard Water D at 30 2 C. 3.3 Suspensibility (MT 184, CIPAC Handbook K, p.142, 2003) (Notes 3 & 4) A minimum of 95% of the imidacloprid content found under 2.2 shall be in suspension after 30 min in CIPAC Standard Water D at 30 2 C. 3.4 Wet sieve test (MT 185, CIPAC Handbook K, p.148, 2003) Maximum: 0.1% retained on a 75 m test sieve. 3.5 Persistent foam (MT 47.2, CIPAC Handbook F, p.152, 1995) (Note 4) Maximum: 40 ml after 1 min. 4 Storage stability 4.1 Stability at 0 (MT 39.3, CIPAC Handbook J, p.126, 2000) C After storage at 0 2 for 7 days, the formulation shall continue to comply C with the clauses for: suspensibility (3.3); wet sieve test (3.4). 4.2 Stability at elevated temperature (MT 46.3, CIPAC Handbook J, p.128, 2000) After storage at 54 2 for 14 days, the determined average active C ingredient content must not be lower than 97% relative to the determined mean content found before storage (Note 5) and the formulation shall continue to comply with the clauses for: pourability (3.1); spontaneity of dispersion (3.2); suspensibility (3.3); wet sieve test (3.4).
Note 1 Before sampling to verify the formulation quality, inspect the commercial container carefully. On standing, suspension concentrates usually develop a concentration gradient from the top to the bottom of the container. This may even result in the appearance of a clear liquid on the top and/or of sediment on the bottom. Therefore, before sampling, homogenize the formulation according to the instructions given by the manufacturer or, in the absence of such instructions, by gentle shaking of the commercial container (for example by inverting the closed container several times). Large containers must be opened and stirred adequately. After this procedure, the container should not contain a sticky layer of non-dispersed matter at the bottom. A suitable and simple method of checking for a non-dispersed sticky layer "cake" is by probing with a glass rod or similar device adapted to the size and shape of the container. All the physical and chemical tests must be carried out on a laboratory sample taken after the recommended homogenization procedure. Note 2 Unless homogenization is carried out carefully, it is possible for the sample to become aerated. This can lead to errors in the determination of the mass per millilitre and in calculation of the active ingredient content (in g/l) if methods other than MT 3.3 are used. If the buyer requires both g/kg and g/l at 20 then in case of dispute the analytical results C, shall be calculated as g/kg.

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Note 3 Chemical assay is the only fully reliable method to measure the mass of active ingredient still in suspension. However, the simpler gravimetric method, MT 168, may be used on a routine basis provided that it has been shown to give equal results to those of chemical assay. In case of dispute, chemical assay shall be the "referee method". Note 4 The mass of sample to be used in the test should be at the highest rate of use recommended by the supplier. Note 5 Samples of the formulation taken before and after the storage stability test should be analyzed concurrently after the test in order to reduce the analytical error.

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IMIDACLOPRID SUSPENSION CONCENTRATE FOR SEED TREATMENT FAO specification 582/FS (April 2006)
This specification, which is PART ONE of this publication, is based on an evaluation of data submitted by the manufacturer whose name is listed in the evaluation report (582/2004). It should be applicable to relevant products of these manufacturers but it is not an endorsement of those products, nor a guarantee that they comply with the specifications. The specification may not be appropriate for the products of other manufacturers. The evaluation report (582/2004) as PART TWO forms an integral part of this publication.

1 Description The material shall consist of a suspension of fine particles of technical imidacloprid, complying with the requirements of FAO/WHO specification 582/TC (April 2006), in an aqueous phase together with suitable formulants, including colouring matter (Note 1). After gentle stirring or shaking, the material shall be homogeneous (Note 2) and is intended for use without dilution. 2 Active ingredient 2.1 Identity tests (582/FS/M/2, CIPAC Handbook K, p.70, 2003) The active ingredient shall comply with an identity test and, where the identity remains in doubt, shall comply with at least one additional test. 2.2 Imidacloprid content (582/FS/M/3, CIPAC Handbook K, p.70, 2003) The imidacloprid content shall be declared (g/kg or g/l at 20 2C, Note 3) and, when determined, the average measured content shall not differ from that declared by more than the following tolerances:
Declared content, g/kg or g/l at 20 2C above 25 up to 100 above 100 up to 250 above 250 up to 500 Note: the upper limit is included in each range Tolerance 10% of the declared content 6% of the declared content 5% of the declared content

3 Physical properties 3.1 pH range (MT 75.3, CIPAC Handbook J, p.131, 2000) The pH of the undiluted aqueous suspension shall be 5 to 9. 3.2 Pourability (MT 148.1, CIPAC Handbook F, p.348, 1995) Maximum "residue": 4%.

Specifications may be revised and/or additional evaluations may be undertaken. Ensure the use of current versions by checking at: http://www.fao.org/ag/agp/agpp/pesticid/.

FAO SPECIFICATIONS AND EVALUATIONS FOR IMIDACLOPRID Page 15 of 38

3.3 Wet sieve test (MT 185, CIPAC Handbook K, p.148, 2003) Maximum: 0.1 % retained on a 75 m test sieve. 3.4 Persistent foam (MT 47.2, CIPAC Handbook F, p.152, 1995) (Note 4) Maximum: 50 ml after 1 min. 4 Storage stability 4.1 Stability at 0 (MT 39.3, CIPAC Handbook J, p.126, 2000) C After storage at 0 2 for 7 days, the formulation shall continue to comply C with the clause for: wet sieve test (3.3). 4.2 Stability at elevated temperature (MT 46.3, CIPAC Handbook J, p.128, 2000) After storage at 54 2 for 14 days, the determined average active C ingredient content must not be lower than 95% relative to the determined average content found before storage (Note 6) and the formulation shall continue to comply with the clauses for: pH range (3.1); pourability (3.2) wet sieve test (3.3).
Note 1 The formulation shall contain a dye or pigment that permanently colours the seed after treatment (red is recommended) and cannot be removed by washing with water. In some countries, there may be a legal requirement that a specific colour shall be used. The same colour must not be used for denaturing seeds to be used as livestock feeding stuffs. Note 2 Before sampling to verify the formulation quality, inspect the commercial container carefully. On standing, suspension concentrates usually develop a concentration gradient from the top to the bottom of the container. This may even result in the appearance of a clear liquid on the top and/or sediment on the bottom. Therefore, before sampling, homogenize the formulation according to the instructions given by the manufacturer or, in the absence of such instructions, gently shake the commercial container (for example by inverting the closed container several times, large containers must be opened and stirred adequately). After this procedure, the container should not contain a sticky layer of non-dispersed matter at the bottom. A suitable and simple method of checking for a non-dispersed sticky layer ("cake") is by probing with a glass rod or similar device adapted to the size and shape of the container. All the physical and chemical tests must be carried out on a laboratory sample taken after the recommended homogenization procedure. Note 3 If the buyer requires both g/kg and g/l at 20 then in case of dispute the analytical results C, shall be calculated as g/kg. Note 4 The test is conducted with the undiluted product. Note 5 Chemical assay is the only fully reliable method to measure the mass of active ingredient still in suspension. However, the simpler gravimetric method, MT 168, may be used on a routine basis provided that it has been shown to give equal results to those of chemical assay. In case of dispute, chemical assay shall be the "referee method". Note 6 Samples of the formulation taken before and after the storage stability test should be analyzed concurrently after the test in order to reduce the analytical error.

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IMIDACLOPRID OIL-BASED SUSPENSION CONCENTRATE FAO specification 582/OD (April 2006)

This specification, which is PART ONE of this publication, is based on an evaluation of data submitted by the manufacturer whose name is listed in the evaluation report (582/2004). It should be applicable to relevant products of these manufacturers but it is not an endorsement of those products, nor a guarantee that they comply with the specifications. The specification may not be appropriate for the products of other manufacturers. The evaluation report (582/2004) as PART TWO forms an integral part of this publication.

1 Description The material shall consist of a stable brownish suspension of fine particles of technical imidacloprid, complying with the requirements of FAO specification 582/TC (April 2006), in an oil phase together with suitable formulants. After shaking or stirring of the sample, the material shall be homogeneous (Note 1) and suitable for dilution in water. 2 Active ingredient 2.1 Identity tests (582/OD/M/2, CIPAC Handbook, Note 2) The active ingredient shall comply with an identity test and, where the identity remains in doubt, shall comply with at least one additional test. 2.2 Imidacloprid content (582/OD/M/2, CIPAC Handbook, Note 2) The imidacloprid content shall be declared (g/kg or g/l at 20 2C, Note 3) and, when determined, the average measured content shall not differ from that declared by more than the following tolerances:
Declared content, g/kg or g/l at 20 2C above 100 up to 250 above 250 up to 500 Note: the upper limit is included in each range Tolerance 6% of the declared content 5% of the declared content

3 Physical properties 3.1 Pourability (MT 148.1, CIPAC Handbook F, p.348, 1995) Maximum residue: 5%.

Specifications may be revised and/or additional evaluations may be undertaken. Ensure the use of current versions by checking at: http://www.fao.org/ag/agp/agpp/pesticid/.

FAO SPECIFICATIONS AND EVALUATIONS FOR IMIDACLOPRID Page 17 of 38

3.2 Dispersion stability (MT 180, CIPAC Handbook H, p.310, 1998) The formulation, when diluted at 30 2 (Note 4) with CIPAC Standard C waters A and D, shall comply with the following:
Time after allowing the dispersion to stand 0h 0.5 h Limits of stability Initial dispersion complete "Cream", maximum: 0.5 ml "Free oil", maximum: trace "Sediment", maximum: 0.1 ml Re-dispersion complete "Cream", maximum: 1 ml "Free oil", maximum: trace "Sediment", maximum: 0.25 ml

24 h 24.5 h

3.3 Wet sieve test (MT 185, CIPAC Handbook K, p.148, 2003) (Note 5) Maximum: 0.2% of the formulation shall be retained on a 75 m test sieve. 3.4 Persistent foam (MT 47.2, CIPAC Handbook F, p.152, 1995) (Note 6) Maximum: 50 ml after 1 min. 4 Storage stability 4.1 Stability at 0 (MT 39.3, CIPAC Handbook J, p.126, 2000) C After storage at 0 2 for 7 days, the formulation shall continue to comply C with the clauses for: dispersion stability (3.2); wet sieve test (3.3); 4.2 Stability at elevated temperature (MT 46.3, CIPAC Handbook J, p.128, 2000) After storage at 54 2C for 14 days, the determined average active ingredient content must not be lower that 95% relative to the determined average content found before storage (Note 7) and the formulation shall continue to comply with the clauses for: pourability (3.1); dispersion stability (3.2); wet sieve test (3.3).
Note 1 Before sampling to verify the formulation quality, inspect the commercial container carefully. On standing, suspension concentrates usually develop a concentration gradient from the top to the bottom of the container. This may even result in the appearance of a clear liquid on the top and/or sediment on the bottom. Therefore, before sampling, homogenize the formulation according to the instructions given by the manufacturer or, in the absence of such instructions, gently shake the commercial container (for example by inverting the closed container several times, large containers must be opened and stirred adequately). After this procedure, the container should not contain a sticky layer of non-dispersed matter at the bottom. A suitable and simple method of checking for a non-dispersed sticky layer ("cake") is by probing with a glass rod or similar device adapted to the size and shape of the container.

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All the physical and chemical tests must be carried out on a laboratory sample taken after the recommended homogenization procedure. Note 2 Extension of the methods for the identification and determination of imidacloprid content in OD were adopted by CIPAC in 2004 but are not yet published in a Handbook. The basic method for determination of imidacloprid (in TC, WG, SC, WS, FS) was published in CIPAC Handbook K (2003). Prior to publication of the Handbook, copies of the methods may be obtained through the CIPAC website, http://www.cipac.org/prepubme.htm or from the CIPAC Secretary, Dr Lszl Bura (mail to [email protected]). Note 3 If the buyer requires both g/kg and g/l at 20 then in case of dispute the analytical results C, shall be calculated as g/kg. Note 4 The formulation should be tested at 2% dilution or, alternatively, at the highest and lowest rates of use recommended by the supplier. Note 5 This test detects coarse particles (e.g. caused by crystal growth) or agglomerates (crust formation) or extraneous materials which could cause blockage of spray nozzles or filters in the spray tank. Note 6 The mass of sample to be used in the test should be at the highest rate of use recommended by the supplier. Note 7 Samples of the formulation taken before and after the storage stability test should be analyzed concurrently after the test in order to reduce the analytical error.

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IMIDACLOPRID SOLUBLE CONCENTRATE FAO specification 582/SL (April 2006)

This specification, which is PART ONE of this publication, is based on an evaluation of data submitted by the manufacturer whose name is listed in the evaluation report (582/2004). It should be applicable to relevant products of these manufacturers but it is not an endorsement of those products, nor a guarantee that they comply with the specifications. The specification may not be appropriate for the products of other manufacturers. The evaluation report (582/2004) as PART TWO forms an integral part of this publication.

1 Description The material shall consist of technical imidacloprid, complying with the requirements of FAO specification 582/TC (April 2006), dissolved in suitable solvents, together with any other necessary formulants. It shall be in the form of a clear or opalescent liquid, free from visible suspended matter and sediment, to be applied as a true solution of the active ingredient in water. 2 Active ingredient 2.1 Identity tests (CIPAC 582/SL/M2, CIPAC Handbook, Note 1) The active ingredient shall comply with an identity test and, where the identity remains in doubt, shall comply with at least one additional test. 2.2 Imidacloprid content (CIPAC 582/SL/M3, CIPAC Handbook, Note 1) The imidacloprid content shall be declared (g/kg or g/l at 20 2C, Note 2) and, when determined, the average measured content shall not differ from that declared by more than the following tolerances:
Declared content, g/kg or g/l at 20 2C above 25 up to 100 above 100 up to 250 Note: the upper limit is included in each range Tolerance 10% of the declared content 6% of the declared content

3 Physical properties 3.1 Solution stability (MT 41, CIPAC Handbook F, p.131, 1995) The formulation, after the stability test at 54C (clause 4.2) and following dilution (Note 3) with CIPAC standard water D and standing at 30 2C for 18 h, shall give a clear or opalescent solution, free from more than a trace of sediment and visible solid particles. Any visible sediment or particles produced shall pass through a 45 m test sieve.

Specifications may be revised and/or additional evaluations may be undertaken. Ensure the use of current versions by checking at: http://www.fao.org/ag/agp/agpp/pesticid/.

FAO SPECIFICATIONS AND EVALUATIONS FOR IMIDACLOPRID Page 20 of 38

3.2 Persistent foam (MT 47.2, CIPAC Handbook F, p.152, 1995) (Note 3) Maximum: 5 ml after 1 minute. 4 Storage stability 4.1 Stability at 0 (MT 39.3, CIPAC Handbook J, p.126, 2000) C After storage at 0 2 for 7 days, the volume of solid and/or liquid which C separates shall not be more than 0.1 ml. 4.2 Stability at elevated temperature (MT 46.3, CIPAC Handbook J, p.128, 2000) After storage at 54 2 for 14 days, the determined average active C ingredient content must not be lower than 97 % relative to the determined average content found before storage (Note 5).
Note 1 Extension of the methods for the identification and determination of imidacloprid content in OD were adopted by CIPAC in 2004 but are not yet published in a Handbook. The basic method for determination of imidacloprid (in TC, WG, SC, WS, FS) was published in CIPAC Handbook K (2003). Prior to publication of the Handbook, copies of the methods may be obtained through the CIPAC website, http://www.cipac.org/prepubme.htm or from the CIPAC Secretary, Dr Lszl Bura (mail to [email protected]). C, Note 2 If the buyer requires both g/kg and g/l at 20 then in case of dispute the analytical results shall be calculated as g/kg. Note 3 The concentration used for the test should not be higher than the highest concentration recommended in the instructions for use. Note 4 The mass of sample to be used in the test should correspond to the highest rate of use recommended by the supplier. Note 5 Samples of the formulation taken before and after the storage stability test should be analyzed concurrently after the test in order to reduce the analytical error.

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PART TWO EVALUATION REPORTS

IMIDACLOPRID Page 2004 FAO/WHO evaluation report based on submission of information from Bayer CropScience (TC, GR, WS, WG, SC, FS, OD, SL) Supporting information Annex 1: hazard summary provided by the proposer Annex 2: references 2008 Addendum Report based on submission of information from Cheminova A/S (FAO Specification 582/GR)

22 24 29 33 36

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IMIDACLOPRID FAO/WHO EVALUATION REPORT 582/2004 Recommendations The Meeting recommended the following. (i) The specifications for imidacloprid TC, GR, WG, WS, SC, FS, OD and SL, proposed by Bayer CropScience AG, as amended, should be adopted by FAO. (ii) The manufacturer should resubmit a draft specification for imidacloprid DT when validated test methods and agreed guidelines become available for tablet integrity. Appraisal The Meeting considered data on imidacloprid, submitted by Bayer AG/Bayer CropScience AG, for the development of new FAO specifications for TC, GR, WS, WG, SC, FS, OD and SL. A draft specification for DT was also submitted but, in the absence of suitable test methods and agreed characteristics for tablet integrity, this was not considered further. The data and proposed specifications were broadly in accordance with the requirements of the FAO/WHO manual. Imidacloprid is under patent till 2006. Imidacloprid is an off-white powdered solid, of very low volatility. It has slight solubility in water, which is not influenced by pH, but is not fat-soluble. It is not measurably acidic or basic; it is stable at pH 4 and 7 and only very slowly hydrolyzed at pH 9. In contrast, it is subject to very rapid photolysis, which forms a major route of dissipation in the environment. Confidential information on the method of manufacture, the technical specification and data from the analysis of production batches was presented to the meeting. Mass balances in the batch analyses were high (99.6-99.7%). The data presented were confirmed as identical to those submitted for registration in Europe (Germany is rapporteur member state for the re-evaluation and authorization of imidacloprid in the European Union under the provisions of directive 91/414/EEC). The Meeting agreed that none of the impurities should be considered as relevant. Analytical methods for imidacloprid (including identity tests) in TC, GR, WG, WS, SC, FS, OD, SL are full CIPAC methods. The method for GR was published in CIPAC Handbook H. The methods for TC, WG, WS, SC, FS were published in CIPAC handbook K and extensions to OD and SL were adopted by CIPAC 2004 but are not yet published. In these methods, imidacloprid is determined by reversed-phase HPLC, using external standardization and detection at 260 nm. The method for determination of impurities was also based on reversed-phase HPLC, using isocratic elution, UV-detection and external standardization with authentic standards.

FAO SPECIFICATIONS AND EVALUATIONS FOR IMIDACLOPRID Page 23 of 38

Test methods for determination of physico-chemical properties of the technical active substance were OECD, USEPA, EC, while those for the formulations were for example, CIPAC, as indicated in the specifications. The physical properties, the methods for testing them and the limits proposed for the GR, WS, WG, SL, SC and OD specification, as amended following discussions between the Meeting and manufacturer, comply with the requirements of the FAO/WHO Manual. The proposed specification for FS did not incorporate a clause for suspensibility, because the manufacturer explained that the product is not intended for dilution with water before use. The Meeting agreed that the clause was inappropriate in this case, that the description clause should be amended to reflect this, and that the test for persistent foam should be conducted on the undiluted product. The manufacturer noted that the red dye in the undiluted FS tends to make the exact determination of persistent foam more difficult than is usual with method MT 47.2 but stated that the product does comply with the specification.

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SUPPORTING INFORMATION FOR EVALUATION REPORT 582/2004

FAO SPECIFICATIONS AND EVALUATIONS FOR IMIDACLOPRID Page 25 of 38

Uses Imidacloprid is a chloronicotinyl (also known as neonicotinoid) insecticide with a broad spectrum of contact and ingestion activity against insects but with no activity against spider mites or nematodes. It is used against sucking insects (such as aphids, whiteflies, leaf-hoppers, thrips, scales, mealy bugs, psyllids, phylloxera), phytophagous coleoptera (such as Colorado beetles, rice water weevils, wireworms, beetle grubs, flea beetles), and various other pests (such as lepidopterous leafminers, some dipterous pests, termites, locusts and fleas). It is systemic in plants, has significant residual activity, and controls pests which are resistant to other classes of insecticide. Imidacloprid interferes with the transmission of nerve impulses in insects. As with the naturally occurring signal-transmitter acetylcholine, imidacloprid stimulates nerve cells by acting on a receptor protein. In contrast to acetylcholine, which is quickly degraded by the enzyme acetylcholine-esterase, imidacloprid is inactivated either very slowly or not at all. Pest feeding activity ceases within minutes to hours and death occurs usually within 24-48 hours but can take up to a few days. Identity of the active ingredient ISO common names Imidacloprid (BSI, E-ISO), imidaclopride ((m) draft F-ISO) Synonyms BAY NTN 33 893 Chemical names IUPAC 1-(6-chloro-3-pyridinylmethyl)-N-nitroimidazolidin-2-ylideneamine CA 1-[(6-chloro-3-pyridinyl)methyl]-N-nitro-2-imidazolidinimine
NO2

Structural formula
N N NH Cl N

Empirical formula C9H10ClN5O2 Relative molecular mass 255.7 CAS Registry number 138261-41-3 CIPAC number 582 Identity tests HPLC retention time, IR and 1H-NMR spectra.

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Physical and chemical properties

Table 1.
Characteristic

Physicochemical properties of pure imidacloprid

Value
-10

Vapour pressure 4 x 10 Pa at 20C -10 9 x 10 Pa at 25C Melting point 144C 99.9 Boiling point Not measurable Decomposition DTA-measurement: 99.5 temperature No exothermic decomposition occurred below 150 C. TGA-measurement: Above 230 a weight loss was observed C, both under air and under a nitrogen atmosphere. Imidacloprid is thermally stable at room temperature. 0.61 g/l at 20 C Solubility is not influenced by pH in the range pH 4 to 9. POW = 3.7 Log POW = 0.57 at 21 C Effect of pH not investigated because pH (49) does not influence water solubility. Imidacloprid was found to be stable with a half-life > 1 year at pH 5 and 7. Slow hydrolysis with a half-life of approx. 1 year occurred at pH 9. Half-life = 57 min. at 5.4 mg/l, 23 to 24.5 C, sterile conditions, irradiated with xenon lamp and UV-glass filter (cut-off 290 nm). The corresponding rate constant was 0.012 min 1 . Environmental half-life in surface water calculated as 4.2 h, at 50 latitude (e.g. N. Germany) and at the equinox. Imidacloprid shows very weakly basic properties. Complete protonation can be achieved only in non-aqueous solutions in presence of very strong acids. It is not possible to determine a pK value in pure aqueous systems.

Purity, % 99.9

Method

Reference

OECD 104, by PC313 extrapolation OECD 102 OECD 113 PC312 PC14376 PC339

Solubility in water Octanol:water partition coefficient Hydrolysis

97.2

EEC A6 OECD 105 EEC A8 OECD 107

PC320

99.8

PC337

>99.8

EPA 161-1

NR1276

Photolysis

>99.8

EPA 161-2

PF3517

Dissociation characteristics

99.8

OECD 112

PC317

Table 2. Chemical composition and properties of imidacloprid technical material (TC)

Manufacturing process, maximum limits for impurities 1 g/kg, 5 batch analysis data. Declared minimum imidacloprid content: Relevant impurities 1 g/kg and maximum limits for them: Relevant impurities < 1 g/kg and maximum limits for them: Confidential information supplied and held on file by FAO. Mass balances were 99.6 99.7%. 970 g/kg None None

FAO SPECIFICATIONS AND EVALUATIONS FOR IMIDACLOPRID Page 27 of 38

Table 2. Chemical composition and properties of imidacloprid technical material (TC)

Stabilizers or other additives and maximum None limits for them: Melting temperature range (TC) 142-144 C

Background information on toxicology/ecotoxicology Bayer CropScience confirmed that the toxicological and ecotoxicological data included in Annex 1, below, were derived from imidacloprid having impurity profiles similar to those referred to in Table 2, above. Imidacloprid was evaluated for toxicology by the FAO/WHO JMPR in 2001, which set the reference doses: ADI: 0.06 mg/kg bw/day; acute RfD: 0.4 mg/kg bw. Imidacloprid was evaluated for residues by the FAO/WHO JMPR in 2002, which recommended MRLs for 51 food commodities and assessed the dietary risks from long- and short-term intake of residues as "unlikely to present a public health concern". Imidacloprid was evaluated by the U.S. EPA in 1992/93 and the results (imidacloprid compound (BAY NTN 33893 Techn.) Registry No. EPA 3125-414, approval March 18, 1994) were published in the U.S. Federal Register in 1994. Residue tolerances were established (USEPA 1996). The Bayer CropScience hazard phrases and classification are: Harmful if swallowed Harmful to aquatic organisms Do not breathe dust Classification: Xn: harmful Harmful to honeybees by direct contact, but no problems expected when not sprayed into flowering crop or when used as seed treatment. The WHO hazard classification of imidacloprid is Class II, moderately hazardous (WHO 2002). Formulations Imidacloprid is registered and marketed world-wide for use in more than 120 countries and on over 160 crops. The main formulation types are SL, SC, WG, WS and FS. Methods of analysis and testing The analytical methods for imidacloprid (including identity tests) in TC, GR, WG, WS, SC, FS, OD, SL are full CIPAC methods. The method for GR was published in CIPAC Handbook H. The methods for TC, WG, WS, SC, FS were published in CIPAC handbook K; extensions to OD and SL were adopted by CIPAC 2004 but are not yet published. In these methods, imidacloprid is determined by reversed-phase HPLC, using external standardization and detection at 260 nm. The analytical method for determination of impurities (Bayer method 2201-030870298) is also based on reversed-phase HPLC, using isocratic elution and UV-detection

FAO SPECIFICATIONS AND EVALUATIONS FOR IMIDACLOPRID Page 28 of 38

with certified reference substances for external standard calibration. reports were provided.

Validation

Test methods for determination of physico-chemical properties of the technical active substance were OECD, USEPA or EC, while those for the formulations were CIPAC, as indicated in the specifications. Containers and packaging No special requirements for containers and packaging have been identified. Expression of active ingredient The active ingredient is expressed as imidacloprid, in g/kg in solid formulations, and in g/kg or g/l at 20 2C in liquid formulations.

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ANNEX 1 HAZARD SUMMARY PROVIDED BY THE PROPOSER Note: The proposer provided written confirmation that the toxicological and ecotoxicological data included in the following summary were derived from imidacloprid having impurity profiles similar to those referred to in Table 2, above.

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Table A. Toxicology profile of the imidacloprid technical material, based on acute toxicity, irritation and sensitization
Species Rat (m,f) Rat Rat Rabbit Test oral dermal inhalation skin irritation Duration and conditions single application; OECD 401, purity: 94.2% single application 24 h; OECD 402, purity: 94.2% dust, 4 h exposure; OECD 403, purity: 95.3% OECD 404, duration of exposure: 4 hours, purity: 94.2% OECD 405, duration of exposure: 24 hours, purity: 94.2% Maximization test, purity: 94.2% Result Reference LD50 = 424 mg/kg bw (m) 18594 450 mg/kg bw (f) LD50 >5000 mg/kg bw 18594 LC50 >5323 mg/m non-irritating
3

16777 16455

Rabbit

eye irritation

non-irritating

16456

Guinea pig skin sensitization

non-sensitizing

16533

Table B. Toxicology profile of imidacloprid technical material based on repeated administration (sub-acute to chronic)
Species Rabbit Rat Dog Rat Rat Mouse Dog Rat Mouse Dog Rat Test sub-acute, dermal sub-acute, inhalation sub-acute, feeding sub-chronic, feeding sub-chronic, feeding sub-chronic, feeding sub-chronic, feeding chronic/oncogenicity , feeding Duration and conditions OECD 410, purity: 95.0% OECD 412, purity: 95.2% OECD 409, 4 weeks, purity: 92.8% OECD 408, 13 weeks, purity: 92.8% OECD 408, 13 weeks, purity: 95.3% OECD 408, 13 weeks, purity: 92.8% OECD 409, 13 weeks, purity: 95.3% OECD 453, 24 months, purity: 94.3-95.3% Result NOAEL = 1000 mg/kg bw/day NOAEC = 5.5 mg/m air NOAEL = 7.3 mg/kg bw/day NOAEL = 11 mg/kg bw/day NOAEL = 14 mg/kg bw/day NOAEL = 17 mg/kg bw/day NOAEL = 7.8 mg/kg bw/day Reference 19152 18199 R4196 17279 18187 17280 18732 19925 19931; 20769 R4856 R5097

Rat (f)

NOAEL = 5.7 mg/kg bw/day Not carcinogenic oncogenicity, OECD 451, 24 months, NOAEL = 65.5 mg/kg bw/day feeding purity: 95.3% Not carcinogenic chronic, feeding OECD 452, 52 weeks, NOAEL = 15 mg/kg bw/day purity: 94.9% 2-generation OECD 416, purity: NOAEL parents = 6.7 mg/kg bw/day, reproduction toxicity 94.4-95.3% NOAEL developmental = 12.5 mg/kg bw/day developmental OECD 414, purity: NOAEL maternal = 10 mg/kg bw/day, toxicity 94.2% NOAEL developmental = 30 mg/kg bw/day, Not teratogenic

R5442

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Table B. Toxicology profile of imidacloprid technical material based on repeated administration (sub-acute to chronic)
Species Test Rabbit (f) developmental toxicity Duration and conditions Result OECD 414, purity: NOAEL maternal = 8 mg/kg bw/day, 94.2% NOAEL developmental = 24 mg/kg bw/day, Not teratogenic Reference R5443

Table C. Mutagenicity profile of imidacloprid technical material based on in vitro and in vivo tests
Species Salmonella microsome Test Conditions Reverse mutation, in OECD 471, doses: 0-20-100-500vitro 2500-12500 g/plate, purity: 95.0% Reverse mutation, in OECD 471, doses: 0-8-40-200Salmonella vitro 1000-5000 g/plate, purity: 96.0microsome 96.3% Reverse mutation, in OECD 471, doses: 0-8-40-200Salmonella vitro microsome 1000-5000 g/plate, purity: 97.4% Reverse mutation, in OECD 471, doses: 0-312.5-625Salmonella vitro 1250-2500-5000 g/plate, purity: microsome 93.7% Bacillus subtilis Recombinant assay, in compliance with MAFF (59 in vitro Nousan No. 4200), doses: 0312.5-625-1250-2500-5000 g/plate, purity: 94.7% in vitro CHO-HGPRT OECD 476, doses: up to 125 g/ml with S-9 mix and 1222 g/ml without S-9 mix, purity: 95.2% Saccharomyces Mitotic OECD 480, doses: 0-625-1250recombination, in 2500-5000-10000 g/ml, purity: cerevisiae vitro 95.3% UDS test, in vitro Rat primary OECD 482, doses: 750 g/ml to hepatocytes 5.00 g/ml, purity: 95.2% Chinese hamster Sister chromatid OECD 473, doses: up to and exchange, in vitro ovary cells including 5000g/ml, purity: 95.2% Chinese hamster Sister chromatid OECD 473, doses: up to 400 ovary cells exchange, in vitro g/ml without S-9 mix and up to 1250 g/ml with S-9 mix, purity: 95.2% Human lymphocyte Cytogenetic study, in OECD 473, up to 5200 g/ml, vitro purity: 95.2% Chinese hamster Cytogenetic study, in OECD 475, dose: 2000 mg/kg, bone marrow vivo purity: 94.6% Mouse marrow bone Micronucleus test, in OECD 474, dose: 80 mg/kg, vivo purity: 95.3% OPPTS 8705915, doses: 5001000-2000 mg/kg, purity: 95.0% Result negative Reference 17577

negative

20090

negative negative

21775 RA91002

negative

RA90016

negative

17578

negative

16832

negative weakly positive negative

R4631 R4407 BC1149

positive negative negative negative negative

18092 18557 16837 18093 R5063

Chinese hamster Sister chromatid bone marrow exchange, in vivo Mouse germ-cell

Cytogenetic study, in OECD 483, dose: 80 mg/kg vivo

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Table D. Ecotoxicology profile of imidacloprid technical material

Species Leuciscus idus melanotus (golden orfe) Oncorhynchus mykiss (rainbow trout) Daphnia magna (water flea) Daphnia magna (water flea) Chironomus riparius (midge larvae) Selenastrum capricornutum (green alga) Earthworm Earthworm Test acute Duration and conditions Result 96h, 21C, purity: 95.3% LC50 = 237 mg a.s./l 96h, 21C, purity: 95.3% LC50 = 211 mg a.s./l 48h, 20C static, purity: 95.4% 21 d, 20 C static renewal, purity: 95.4% 28 d, 20 C static, purity: 98.4% 72h, 23C, static, purity: 98.6% EC50 = 85 mg/l Reference FO-1042

acute

FF-210

acute chronic

100245

NOEC = 1.8 mg/l 100247

chronic

EC15 = 0.00225 mg/l ErC50 >100 mg/l LOEC <100 mg/l

DOM 21035

chronic

DOM 20018

Apis mellifera (honey bee)

Apis mellifera (honey bee) Bobwhite quail Bobwhite quail

Bobwhite quail Mallard duck

Mallard duck Mallard duck Japanese quail Japanese quail

14d, 22C, purity: 92.8% LC50 = 10.7 mg/kg dry soil chronic toxicity reproduction, 8 wks, NOEC 0.178 mg/kg purity: 98.6% (5 % O.M.) acute oral 48h, purity: 98.6% LD50 >21 ng/bee toxicity 48h and 96h, LD50 = purity: 99.4% 40.9 ng/bee 48h, purity: 99.8% LD50 = 3.7 ng/bee acute contact 72h, purity: 98.6% LD50 = 129 ng/bee toxicity 48h, 99.8% LD50 = 81 ng/bee acute toxicity 14d, single dose, LD50 = purity: 97.4% 152 mg a.s./kg bw sub-acute 5d, purity: 98.4% LC50 = 2225 ppm feed toxicity (14d) LC50 >5000 ppm feed (adult) sub-chronic 20 wks, reproduction, NOEC = toxicity purity: 94.8% 126 ppm feed acute oral 14d, single dose, LD50 = 283 mg a.s./kg toxicity purity: 96.6% b.w. sub-acute 5d, purity: 97.4% LC50 >4797 ppm toxicity feed sub-chronic 20 wks, reproduction, NOEC = toxicity purity: 95.8%. 128 ppm feed acute oral 14d, single dose, LD50 = toxicity purity: 95.3% 31 mg a.s./kg b.w. sub-acute 5d, purity: 97.2% LC50 = toxicity 392 ppm feed

acute toxicity

HBF/RG 63 HBF/RG 301

AH99.4.22.4 6400036 BAY 158/901384 AH99.4.22.3 BAY 158/901384 100059 SXR/VB 57

101203 107354

100238 103813-1 VW-123 GMU/VW-177

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Annex 2. References
Bayer CropScience document number 100059 100238 100245 100247 101203 103813-1 107354 16455 16456 16533 16777 16832 16837 17279 17280 17577 17578 18092 18093 18187 18199 18557 18594 18732 19152 19925 Year and title of report or publication details 1990. Technical NTN 33893: An acute oral LD50 with Bobwhite quail. 1990. Technical NTN 33893: A subacute dietary LC50 with Mallard ducks. 1990. Acute Toxicity of NTN 33893 to Daphnia magna. 1990. 21-Day Chronic Static Renewal Toxicity of NTN 33893 to Daphnia magna. 1991. Technical NTN 33893: A One Generation Reproduction Study with Bobwhite Quail. 1993. Technical NTN 33893: A One Generation Reproduction Study With Mallard Ducks. 1996. NTN 33893 Technical: An acute oral LD50 with Mallards. 1988. NTN 33893 - Study for irritant/corrosive potential on the skin (rabbit) according to OECD guideline no. 404. 1988. NTN 33893 - Study for irritant/corrosive potential on the eye (rabbit) according to OECD guideline no. 405. 1988. NTN 33893 technical - Study for skin sensitising effect on guinea pigs (maximisation test). 1988. NTN 33893 - Study for acute inhalation toxicity in the rat in accordance with OECD guideline no. 403. 1988. NTN 33893 - Test on S. cerevisiae D7 to evaluate for induction of mitotic recombination.. 1988. NTN 33893 - Micronucleus-test on the mouse to evaluate for clastogenic effects. 1988. NTN 33893 - Pilot range-finding study for a chronic toxicity study on Wistar rats (ninety-eight day feeding study). 1988. NTN 33893 - Pilot range-finding study for a cancerogenesis study on B6C3F1 mice (one hundred seven day feeding study). 1989. NTN 33893 - Salmonella/microsome test to evaluate for point mutagenic effects. 1989. NTN 33893 - Mutagenicity study for the detection of induced forward mutations in the CHO-HGPRT assay in vitro. 1989b. NTN 33893 - In vitro cytogenetic study with human lymphocytes for the detection of induced clastogenic effects. 1989. NTN 33893 - Sister chromatid exchange in bone marrow of chinese hamsters in vivo. 1989. NTN 33893 - Subchronic toxicity study on wistar rats (administration in the feed for 96 days). 1989. NTN 33893 (proposed common name: Imidacloprid) - Subacute inhalation toxicity study on the rat according to OECD guideline no. 412. 1989. NTN 33893 - In vivo cytogenetic study of the bone marrow in chinese hamster to evaluate for induced clastogenic effects. 1989. NTN 33893 - Study for acute oral toxicity to rats. 1990. NTN 33893 technical - Subchronic toxicity study on dogs in oral administration (thirteen-week feeding study). 1990. NTN 33893 techn. - Study for subacute dermal toxicity in the rabbit. 1991. NTN 33893 (proposed c.n.: Imidacloprid) - Chronic toxicity and cancerogenicity studies on Wistar rats (administration in food over 24 months). 1991. NTN 33893 (proposed common name Imidacloprid) - Carcinogenicity study on B6C3F1 mice (administration in the food for 24 months). 1991. NTN 33893 AMP - Salmonella/microsome test.

19931 20090

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Bayer CropScience document number 20769

Year and title of report or publication details 1991. NTN 33893 (proposed common name: Imidacloprid) - Carcinogenicity study in B6C3F1 mice (supplementary MTD testing for study T5025710 with administration in diet over a 24-month period). 1992. NTN 33893 AMP W - Salmonella/microsome test. 1999. Laboratory Testing for Toxicity (Acute Oral LD50) of NTN 33893 on Honey Bees (Apis mellifera L.) (Hymenoptera, Apidae). 1999. Honeybee (Apis mellifera L.) Contact Toxicity Study in the Laboratory with Imidacloprid techn. 1999. Honeybee (Apis mellifera L.) Oral Toxicity Study in the Laboratory with Imidacloprid techn. 1990. The Acute Oral and Contact Toxicity to Honey Bees of Compound NTN 33893 Technical. 1989. BAY NTN 33893 - Sister chromatid exchange assay in chinese hamster ovary cells. Dobrat, W. and Martijn, A. Eds. (1998): CIPAC Handbook volume H, Analysis of technical and formulated pesticides. Collaborative International Pesticides Analytical Council, Harpenden, U.K. Dobrat, W. and Martijn, A. Eds. (2003). CIPAC Handbook volume K, Analysis of technical and formulated pesticides. Collaborative International Pesticides Analytical Council, Harpenden, U.K. 2000. Imidacloprid - Influence on the Growth of the Green Alga, Selenastrum capricornutum. 2001. Influence of Imidacloprid (tech.) on Development and Emergence of Larvae of Chironomus riparius in a Water-Sediment System. Manual of the development and use of FAO and WHO specifications for pesticides. FAO plant production and protection paper 173. FAO, Rome, 2002. 1988b. The acute toxicity of NTN 33893 techn. to Rainbow trout (Salmo gairdneri) in a static test. 1987. The Acute Toxicity of NTN 33893 techn. to Golden Orfe (Leuciscus idus melanotus) in a Static Test. 1996. NTN 33893 techn.: 5-Day Dietary LC50 to Japanese quail. 1999. Influence of Low Concentrations of Imidacloprid (tech.) on the Reproduction of Earthworms (Eisenia fetida). 1986. Acute toxicity of NTN 33893 (tech.) to earthworms. 1989. Hydrolysis of NTN 33893. 1996. Boiling Point of Imidacloprid (NTN 33893). 1993. Melting Point of Imidacloprid 1993. Vapour Pressure Curve of Imidacloprid. 1990. Dissociation constant of NTN 33893. 1993. Water solubility of Imidacloprid. 1989. Octanol/Water partition coefficient of NTN 33893. 1998. Thermal stability of the active ingredient NTN 33893. 1988. Photodegradation of NTN 33893 in water. 1987. 28-day oral range-finding toxicity (feeding) study with NTN 33893 tech. in the dog. 1988. Clastogenic evaluation of NTN 33893 in an in vitro cytogenetic assay measuring sister chromatid exchange in chinese hamster ovary (CHO) cells. 1988. Mutagenicity test on NTN 33893 in the rat primary hepatocyte unscheduled DNA synthesis assay. 1989. 52-week oral toxicity (feeding) study with NTN 33893 technical in the dog. 1990. Mouse germ-cell cytogenetic assay with NTN 33893.

21775 6400036 AH99.4.22.3 AH99.4.22.4 BAY 158/901384 BC1149 CIPAC H

CIPAC K

DOM 20018 DOM 21035 FAO/WHO 2002

FF-210 FO-1042 GMU/VW-177 HBF/Rg 301 HBF/Rg 63 NR1276 PC1437 PC312 PC313 PC317 PC320 PC337 PC339 PF3517 R4196 R4407 R4631 R4856 R5063

FAO SPECIFICATIONS AND EVALUATIONS FOR IMIDACLOPRID Page 35 of 38

Bayer CropScience document number R5097 R5442 R5443 RA90016 RA91002 SXR/VB 57 USEPA 1996 VW-123 WHO 2002

Year and title of report or publication details 1990. Multiple generation reproduction study with NTN 33893 technical in rats. 1998. Embryotoxicity study (including teratogenicity) with NTN 33893 technical in the rat. 1988. Embryotoxicity study (including teratogenicity) with NTN 33893 technical in the rabbit. 1990. NTN 33893 - Rec-assay with spores in the bacterial System. 1991. NTN 33893 - Reverse mutation assay (Salmonella typhimurium and Escherichia coli). 1996. Age-related five day dietary toxicity of imidacloprid to Bobwhite quail. Pesticide tolerances. Imidacloprid. Federal Register, February 14, 1996, Vol. 61, No. 31 [Rules and Regulations], pages 5711 ff. 1988. Acute oral LD50 of NTN 33893 to Japanese quail. The WHO recommended classification of pesticides by hazard and guidelines to classification 2000-2002. WHO, Geneva, 2002.

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Addendum Report
(FAO Specification 582/GR/2008) (CIPAC number 582) Explanation Imidacloprid data were provided in 2004 by Bayer CropScience to support specifications for imidacloprid TC, GR, WS, WG, SC, FS, OD, SL. The FAO specifications were published in 2006. Supporting data for the extension of an existing specification (imidacloprid GR) were provided by Cheminova A/S in 2007. The Cheminova A/S granular formulations are prepared from Bayer CropScience technical material that complies with FAO specifications. The Cheminova A/S granular formulations do not meet the existing GR specifications in two respects:
- colour of the granules; and - upper limits for pour and tap density.

Data were provided to support proposed changes to the existing specifications for imidacloprid granules. Recommendations The Meeting recommended that:
- the specifications for imidacloprid GR be amended to include coloured granules and to accommodate wider ranges for pour and tap density.

Appraisal Imidacloprid specifications for TC, GR, WS, WG, SC, FS, OD and SL were published in 2006 after a data submission from Bayer CropScience. In 2007, Cheminova A/S requested an extension of the imidacloprid GR specification and provided supporting data. The extension involves a change in description from "beige granules" to "beige or coloured" granules and to allow a wider range in pour and tap densities (upper limits to increase by 0.1 g/ml).

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The granules from both manufacturers are manufactured from the same source of TC, but possibly different carrier materials, which may influence the density. The colouring is to assist observation of the granules on soil. Neither change should influence the product performance. SUPPORTING INFORMATION Formulations and co-formulated active ingredients The main formulation types available are SL, SC, WG, GR, FS and WS. In GR formulations, imidacloprid may be formulated alone or co-formulated with other active ingredients, such as organophosphate and pyrethroid insecticides. Cheminovas imidacloprid GR formulations are registered and sold in Great Britain. Methods of analysis and testing Analytical methods for the active ingredient are based on the methods and testing described in existing FAO specification for imidacloprid GR formulations (FAO Specification 582/GR (May 2006)) following the new procedure. Test methods for determination of physico-chemical properties of the technical active ingredient were not applicable as TC utilized by Cheminova A/S for GR formulations originate from a manufacturer whose specification is already approved, while those for the formulations were CIPAC, as indicated in the specifications. Physical properties The physical properties, the methods for testing them and the limits proposed for the GR formulations, comply with the requirements described in the existing FAO specification for imidacloprid GR formulations (FAO Specification 582/GR (May 2006)) following the new procedure, with the following exceptions: Colour In the existing FAO specification for imidacloprid GR formulations (FAO Specification 582/GR (May 2006)) the material is described as beige granules (Refer to 1. Description, line 4 of FAO Specification 582/GR (May 2006)). It is proposed to change the wording to beige or coloured granules.

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Justification for change: granule formulations consist of a carrier material, such as silica, coated with imidacloprid. One of the uses is for soil treatment, where a colouring of the granules will help identify treated areas.

Density In the existing FAO specification for imidacloprid GR formulations (FAO Specification 582/GR (May 2006)) the density range of the formulations is stated as:
Pour density: 1.4 to 1.5 g/ml Tap density: 1.5 to 1.6 g/ml

when determined in compliance with CIPAC MT 186, Handbook K, p. 151, 2003. It is proposed to extend the limits to:
Pour density: 1.4 to 1.6 g/ml Tap density: 1.5 to 1.7 g/ml

when determined in compliance with CIPAC MT 186, Handbook K, p. 151, 2003. Justification for change: The density of the formulation will to a high degree depend on the carrier material, such as silica. The density of these materials can vary. The limits in the existing FAO specification for imidacloprid GR formulations (FAO Specification 582/GR (May 2006)) are narrow, and the suggested extension will allow for additional suitable carriers to be available for formulation purposes. Containers and packaging No special requirements for containers and packaging have been identified.