HET COLLEGE VOOR DE TOELATING VAN GEWASBESCHERMINGSMIDDELEN EN BIOCIDEN

BIJLAGE II bij het besluit d.d. 4 juni 2010 tot uitbreiding van de toelating van het middel Gazelle, toelatingnummer 12809 N

RISKMANAGEMENT

Contents Page

1. Identity of the plant protection product 2

2. Physical and chemical properties 2

3. Methods of analysis 7

4. Mammalian toxicology 11

5. Residues 18

6. Environmental fate and behaviour 19

7. Ecotoxicology 32

8. Efficacy 47

9. Conclusion 48

10. Classification and labelling 48

1. Identity of the plant protection product

1.1 Applicant

Nisso Chemical Europe GmbH

p/a Certis Europe B.V.

Safariweg 55

3605 MA Maarssen

1.2 Identity of the active substance

Common name	acetamiprid
Name in Dutch	acetamiprid
Chemical name	(E)-N’-[(6-chloro-3-pyridyl)methyl]-N²-cyano-N¹-methylacetamidine
CAS no	135410-20-7
EC no	Not allocated

The active substance was included on 1 January 2005 in Annex I of Directive 91/414/EEC.

1.3 Identity of the plant protection product

Name	Gazelle
Formulation type	SG (water soluble granule)
Content active substance	200 g/kg pure a.s. (20%)

The formulation is comparable to the SP formulation included in the DAR. The composition is identical, but the formulation type was changed from a soluble powder to a soluble granule.

1.4 Function

Insecticide.

1.5 Uses applied for

See GAP (appendix 1).

1.6 Background to the application

The application concerns an extension of the authorisation.

1.7 Packaging details

1.7.1 Packaging description

Material:	Polyethylene bottle
Capacity:	1 kg
Type of closure and size of opening:	Opening diameter: 8 cm Plastic screw cap with induction seal
Other information	UN compliant

1.7.2 Detailed instructions for safe disposal

See application form and MSDS (no particular recommendations)

2. Physical and chemical properties

2.1 Active substance: acetamiprid

Data on the identity and the physical and chemical properties is taken from the List of Endpoints included in the final review report on acetamiprid (SANCO/1392/2001 – final, d.d. 16 June 2004). Where relevant, some additional remarks/information are given in italics.

Identity

Active substance (ISO Common Name)	acetamiprid
Chemical name (IUPAC)	(E)-N¹-[(6-chloro-3-pyridyl)methyl]-N²-cyano-N¹-methylacetamidine
Chemical name (CA)	(E)-N-[(6-chloro-3-pyridinyl)methyl]-N’-cyano-N-methylethanimidamide
CIPAC No	Not yet allocated
CAS No	160430-64-8
EEC No (EINECS or ELINCS)	Not yet allocated
FAO Specification (including year of publication)	Not yet allocated
Minimum purity of the active substance as manufactured (g/kg)	990 g/kg
Identity of relevant impurities (of toxicological, environmental and/or other significance) in the active substance as manufactured (g/kg)	No relevant impurities are present in the acetamiprid technical
Molecular formula	C₁₀H₁₁ClN₄
Molecular mass	222.68
Structural formula

Physical-chemical properties

Melting point (state purity)	98.9 ^oC (99.7%)
Boiling point (state purity)	Not relevant^*
Temperature of decomposition	Not relevant^*
Appearance (state purity)	pure a.s. (99.9%): white fine powder, with no characteristic odour technical a.s. (99.9%): very pale yellow fine powder, with no characteristic odour
Relative density (state purity)	Specific gravity (20 ^oC/20 ^oC): 1.330 (99.7%)
Surface tension	70.9 mN/m at 19.5 ^oC
Vapour pressure (in Pa, state temperature)	1.73x10^-7 Pa at 50 ^oC (>99%). Expected <1x10^-6 Pa at 25 ^oC
Henry’s law constant (in Pa·m³·mol^-1)	<5.3x10^-8 Pa m³mol^-1 at 25 ^oC
Solubility in water (in g/l or mg/l, state temperature)	In distilled water: 4.25 g/l at 25 ^oC (>99%) pH 5: 3.48 g/l at 25 ^oC (>99%) pH 7: 2.95 g/l at 25 ^oC (>99%) pH 9: 3.96 g/l at 25 ^oC (>99%)
Solubility in organic solvents (in g/l or mg/l, state temperature)	At 25 ^oC: hexane: 6.54 ppm; xylene: 4.01 g/100 g; benzene: 2.44 g/100g; dichloromethane: >20 g/100g chloroform: >20 g/100 g; methanol: >20 g/100 g; ethanol: >20 g/100 g; acetone: >20 g/100 g; acetonitrile: >20 g/100g; tetrahydrofuran: >20 g/100g; carbone disulfide: 507 ppm (all the above solubility’s are expressed as weight of a.s. per weight of solvent) At 20 ^oC: Ethyl acetate: 37.8 g/l
Partition co-efficient (log P_ow) (state pH and temperature)	log Pow= 0.80 at 25 ^oC (>99%) pH: Not determined (neutral conditions)
Hydrolytic stability (DT₅₀) (state pH and temperature)	pH 4: Stable at 22 ^oC, 35 °C and 45 ^oC pH 5: Stable at 22 ^oC, 35 °C and 45 ^oC pH 7: Stable at 22 ^oC, 35 °C and 45 ^oC pH 9: at 22 ^oC, DT₅₀=812 days at 35 °C, DT50=52.9 days at 45 °C, DT50=13.0 days Calculated at 25 °C: DT50=420 days
Dissociation constant	pKa: 0.7 at 25 ^oC
UV/VIS absorption (max.) (if absorption >290 nm state ε at wavelength)	In neutral medium (CH₃OH/H₂O): λmax : 247 nm, 217 nm ε (M^-1xcm^-1): ε₂₄₇= 1.97x104, ε₂₁₇= 1.21x104
Photostability (DT₅₀) (aqueous, sunlight, state pH)	pH 7: DT₅₀= 34 days under xenon lamp (irradiation: 12 hours/day)
Quantum yield of direct photo- transformation in water at λ > 290 nm	0.10
Photochemical oxidative degradation in air	Half-life at 298K: DT₅₀= 1.679 hours. (Atkinson calculation).
Flammability	Not highly flammable.
Auto-flammability	> 450 ^oC
Oxidative properties	No oxidizing properties.
Explosive properties	Non-explosive.

* These statements have been accepted for inclusion of the active substance in Annex I of guideline 91/414/EEC, but for current standards and regulations these statement are no longer acceptable.

2.2 Plant protection product: Gazelle

Data on the plant protection product is taken from the DAR and addenda. Also new submitted data from applicant is used.

The range of the application concentration of the plant protection product is 0.025 - 0.155%

Section (Annex point)	Study	Guidelines and GLP	Findings	Evaluation and conclusion
B.2.2.1 (IIIA 2.1)	Appearance: physical state	GLP	Free flowing hard granular solid	Acceptable
B.2.2.2 (IIIA 2.1)	Appearance: colour	GLP	Cyan blue	Acceptable
B.2.2.3 (IIIA 2.1)	Appearance: odour	GLP	Weak	Acceptable
B.2.2.4 (IIIA 2.2)	Explosive properties	GLP EEC-A 14	Mechanical sensitivity: - Shock test: negative - Friction test: negative Thermal sensitivity: - Koenen tube: negative Not explosive	Tested for the SP, but also acceptable for the SG
B.2.2.5 (IIIA 2.2)	Oxidising properties	GLP EEC-A17	Product shows no oxidizing properties by testing	Tested for the SP, but also acceptable for the SG
B.2.2.6 (IIIA 2.3)	Flammability	GLP EEC A10	Not highly flammable	Tested for the SP, but also acceptable for the SG
B.2.2.7 (IIIA 2.3)	Auto-flammability	GLP UN-Bowes Cameron Cage test	Product is not flammable but sensitive to self heating at high temperature (>120°C)	Tested for the SP, but also acceptable for the SG
B.2.2.8 (IIIA 2.3)	Flash point		Not applicable
B.2.2.9 (IIIA 2.4)	Acidity / alkalinity		Not applicable
B.2.2.10 (IIIA 2.4)	pH	GLP CIPAC MT 75.2	pH value (1%) : 8.6	Tested for the SP, but also acceptable for the SG
B.2.2.11 (IIIA 2.5)	Surface tension		Not applicable
B.2.2.12 (IIIA 2.5)	Viscosity		Not applicable
B.2.2.13 (IIIA 2.6)	Relative density		Not applicable
B.2.2.14 (IIIA 2.6)	Bulk (tap) density	GLP CIPAC MT 186	Pour density: 0.673 g/ml Tap density: 0.739 g/ml	Acceptable
B.2.2.15 (IIIA 2.7)	Storage stability	GLP CIPAC MT46	No change after storage for 14 days at 54°C in glass: for attrition, content a.s., dilution stability and dust content.
B.2.2.16 (IIIA 2.7)	Shelf life		The SP formulation was stable for 2 years at room temperature in PE packaging.	Acceptable (see below for the shelf-life for the SG formulation).
		GLP GIFAP monograph No. 17	Stable for 2 years at ambient temperatures. Packaging tested: silver opaque foil sachet. Properties determined before and after storage: a.s. content, appearance, wettability, dilution stability, dust content, particle size distribution, friability and attrition, suitability of packaging.	Acceptable study. Packaging tested is not representative for the packaging proposed for the Dutch market. However, a shelf-life study with the same formulation, formulated as a SP instead of SG, is available in polyethylene, which is acceptable in this case.
B.2.2.17 (IIIA 2.8)	Wettability	GLP CIPAC MT53.3.1	The wettability in CIPAC water D is less then 1 s	Acceptable
B.2.2.18 (IIIA 2.8)	Persistent foaming	GLP CIPAC MT47.1	0.1% dilution in CIPAC water D: 7 ml foam after 1 min 1.0% dilution in CIPAC water D: 6 ml foam after 1 min	Acceptable
B.2.2.19 (IIIA 2.8)	Suspensibility		Not applicable
B.2.2.20 (IIIA 2.8)	Spontaneity of dispersion		Not applicable
B.2.2.21 (IIIA 2.8)	Dilution stability	GLP CIPAC MT179	A 1.2% dilution in CIPAC water D showed 0.4% residue (75µm sieve) after 5 min but no residue was observed after 18 hours	Acceptable
B.2.2.22 (IIIA 2.8)	Dry sieve test		See particle size distribution
B.2.2.23 (IIIA 2.8)	Wet sieve test		Statement: because good dilution stability, and the wet sieve test of the SP no test with the SG is required	Acceptable statement
B.2.2.24 (IIIA 2.8)	Particle size distribution	GLP CIPAC MT58.3	Before storage at 54°C/14 days: 0.11% < 150 µm 6.91% < 250 µm After: 0.23% < 150 µm 5.65% < 250 µm	Acceptable
B.2.2.25 (IIIA 2.8)	Content of dust/fines	GLP CIPAC MT171	Nearly dust free (<0.01%)	Acceptable
B.2.2.26 (IIIA 2.8)	Attrition and friability	GLP CIPAC MT178.2	attrition before and after 14 days at 54°C: 99.7%	Acceptable
B.2.2.27 (IIIA 2.8)	Emulsifiability, re-emulsifiability and emulsion stability		Not applicable
B.2.2.28 (IIIA 2.8)	Stability of dilute emulsion		Not applicable
B.2.2.29 (IIIA 2.8)	Flowability	GLP CIPAC MT 172	After storage for 14 days at 54°C all sample falls through the sieve. Free flowing granules	Acceptable
B.2.2.30 (IIIA 2.8)	Pourability (rinsibility)		Not applicable
B.2.2.31 (IIIA 2.8)	Dustability		Not applicable
B.2.2.32 (IIIA 2.8)	Adherence and distribution to seeds		Not applicable
2.9.1	Physical compatibility with other products		Na data, not required as no mixing proposed
2.9.2	Chemical compatibility with other products		Na data, not required as no mixing proposed

Conclusion

The physical and chemical properties of the active substance and the plant protection product are sufficiently described by the available data. Neither the active substance nor the product has any physical or chemical properties, which would adversely affect the use according to the proposed use and label instructions.

2.3 Data requirements

None.

3. Methods of analysis

Description and data on the analytical methods is taken from the List of Endpoints of January 2004. Where relevant, additional remarks/information are given in italics.

3.1. Analytical methods in technical material and plant protection product

Technical as (principle of method)

Samples of acetamiprid technical are dissolved in acetonitrile/water (3:7). Methyl-4-hydroxybenzoate is used as internal standard.

Analysis is carried out by HPLC with UV detection at 255 nm.

Impurities in technical as (principle of method)

Samples of acetamiprid technical are dissolved in acetonitrile/water (3:7). Methyl-4-hydroxybenzoate is used as internal standard.

Analysis is carried out by HPLC with UV detection at 255 nm.

Preparation (principle of method)

Samples of the 20% SP ppp are extracted with acetonitrile. Methyl-4-hydroxybenzoate is used as internal standard.

Analysis is carried out by HPLC with UV detection at 250 nm.

Conclusion

These analytical methods have been assessed in the DAR and are considered to be acceptable.

3.2 Residue analytical methods

Food/feed of plant origin (principle of method and LOQ for methods for monitoring purposes)	i) Multi-residue method (DFG S19 modified): Substrates: apples and tomatoes Extraction: Samples are extracted with acetone/water (2:1) with subsequent extraction with cyclohexane/ethyl acetate (1:1) and partition into acetone/cyclohexane/ethyl acetate. Clean up: The extracts are cleaned up by gel permeation chromatography followed by a silica gel fractionation. Analysis: Analysis is carried out by GC/ECD. GC/MS is used as a confirmatory technique. Determined analyte: acetamiprid LOQ: 0.01 mg/kg for apples 0.05 mg/kg for tomatoes ILV data have been provided for apples and tomatoes. ii) Single method (Studies No. RPA/NI-25/95101N and RPA/NI-25/97062): Substrates: pepper, pear, peach, apple, orange, tomato, cucumber, plum, melon, cotton and tobacco Extraction: Samples are extracted with methanol. Clean up: The extracts are cleaned up over Florisil. Especially for cotton and tobacco samples an additional clean up step over a C18 cartridge and solvent partition (methylene chloride) is necessary. Analysis: Analysis is carried out by GC/ECD. Determined analyte: acetamiprid LOQ: 0.01 mg/kg confirmed only for peach and pepper (Neither confirmatory method nor ILV data have been provided) iii) Single method (Study No. EC-97-388) Substrates: Non citrus fruits and vegetables (cabbage, pears, raisins, cotton seed, cotton gin trash, broccoli, carrot root) Extraction: Samples are extracted with methanol. The extracts are partitioned against hexane and then into methylene chloride. Clean up: The extracts are cleaned up over Florisil and then by column chromatography on 10% deactivated silica gel 60. Analysis: Analysis is carried out by GC/ECD. HPLC/MS and HPLC/MS/MS can be used as confirmatory techniques. Determined analyte: acetamiprid LOQ: 0.01 mg/kg for all substrates Substrates: Citrus (orange whole fruit and orange oil) Extraction: Samples are extracted with acetonitrile and then partitioned against hexane. Clean up: The extracts are cleaned up by chromatography on Florisil and tC-18 reverse-phase columns. Analysis: Analysis is carried out by HPLC/UV. Determined analyte: acetamiprid LOQ: 0.05 mg/kg for both substrates ILV data have been provided for cotton seed.
Food/feed of animal origin (principle of method and LOQ for methods for monitoring purposes)	Substrates: milk, muscle, fat, liver and kidney of ruminant origin and eggs, muscle, fat and liver of hen origin Extraction: Samples are macerated with acetonitrile, with a subsequent partition into hexane and then into dichloromethane. Clean up: The extracts are cleaned up over Florisil and then over a C18 cartridge. Analysis: Analysis is carried out by HPLC-UV. LC/MS/MS is used as a confirmatory technique. Determined analytes: acetamiprid and the metabolite IM-2-1 LOQ: 0.010 mg/kg for milk, muscle, fat, liver, kidney of ruminant origin, muscle of hen origin and eggs for both analytes (Method not required, since no MRLs have been set for products of animal origin)
Soil (principle of method and LOQ)	1) Determination of acetamiprid, IC-0, IM-1-2, IM-1-4: Extraction: Soil samples are extracted with an accelerated solvent extractor (ASE). Clean up: For the determination of the metabolite IM-1-4 the extract is cleaned up using an Extrelut cartridge. Analysis: Analysis is carried out by LC/MS/MS Determined analytes: acetamiprid, IC-0, IM-1-2, IM-1-4 LOQ: 0.01 mg/kg for all the analytes 2) Determination of IM-1-5: Extraction: Soil samples are extracted with an accelerated solvent extractor (ASE). Analysis: Analysis is carried out by LC/MS/MS Determined analyte: IM-1-5 LOQ: 0.01 mg/kg.
Water (principle of method and LOQ)	Extraction: Water samples are extracted by solid phase extraction. Clean up: The extract is cleaned up by chromatography through a C18 cartridge. Analysis: Analysis is carried out by HPLC-UV. GC-MS is used as a confirmatory technique. Determined analyte: acetamiprid LOQ: 0.1 μg/l for drinking, ground and river water
Air (principle of method and LOQ)	Extraction: Acetamiprid is extracted from the adsorbent filled cartridges with acetonitrile with the aid of ultrasonication. Analysis: Analysis is carried out by HPLC-UV. Determined analyte: acetamiprid LOQ: 2 μg/m³
Body fluids and tissues (principle of method and LOQ)	Not applicable. Acetamiprid is not classified as toxic.

Based on the proposed use of the plant protection product analytical methods for determination of residues in food/feed of plant origin are required for watery matrices (cucumber). The intended use for this extension application involves application on ornamentals only.

Definition of the residue and MRL’s for acetamiprid
Matrix	definition of the residue for monitoring	MRL
Food/feed of plant origin	acetamiprid	0.1 mg/kg (apple, pear), 0.2 mg/kg (cherries)
Food/feed of animal origin	Not relevant	No MRL proposed
		Required LOQ
Soil	acetamiprid en metaboliet IM-1-5	0.05 mg/kg
Drinking water	acetamiprid	0.1 µg/L (Dutch drinking water guideline)
Surface water	acetamiprid	0.1 µg/L (HTB 1.0)
Air	acetamiprid	37 µg/m³ (derived from the AOEL according to SANCO/825/00)
Body fluids and tissues	The active substance is not classified as (very) toxic thus no definition of the residue is proposed	Not relevant

The residue analytical methods, included in the abovementioned List of Endpoints, are suitable for monitoring of the MRL’s.

The residue analytical methods for water, soil and air, evaluated in the DAR, are acceptable and suitable for monitoring of residues in the environment.

Conclusion

The submitted analytical methods meet the requirements. The methods are specific and sufficiently sensitive to enable their use for enforcement of the MRL’s and for monitoring of residues in the environment.

3.3 Data requirements

None.

3.4 Physical-chemical classification and labelling

Proposal for the classification of acetamiprid (symbols and R phrases)
(EU classification) concerning physical chemical properties

Symbol(s):

Indication(s) of danger: -

Risk phrase(s)

Proposal for the classification and labelling of the formulation concerning physical chemical properties

Substances, present in the formulation, which should be mentioned on the label by their chemical name (other very toxic, toxic, corrosive or harmful substances):
-
Symbol:	-	Indication of danger:	-
R phrases	-	-
S phrases	S21	When using do not smoke
Special provisions: DPD-phrases	-	-
Child-resistant fastening obligatory?			Not applicable
Tactile warning of danger obligatory?			Not applicable

Explanation:
Hazard symbol:	-
Risk phrases:	-
Safety phrases:	-
Other:	-

In the GAP/instructions for use the following has to be stated:

Not applicable.

4. Mammalian toxicology

List of Endpoints

Acetamiprid is a new active substance, included in Annex I of 91/414/EEC. The final List of Endpoints presented below is taken from the final review report on acetamiprid (SANCO/1392/2001-final, 16 juni 2004). Where relevant, some additional remarks/information are given in italics.

_{Impact on Human and Animal Health}

Absorption, distribution, excretion and metabolism in mammals (Annex IIA, point 5.1)
Rate and extent of absorption:	Rapid and almost complete (> 96% at 24 hrs after single oral administration), Cmax at approximately 0.5-7 hrs after single low and high oral and i.v. administration
Distribution:	Highest concentration adrenal, thyroid, liver and kidney
Potential for accumulation:	Low potential for body accumulation
Rate and extent of excretion:	Rapid and higher than 90% at 96 hrs, mainly via urine, after single and repeated oral administration, regardless of the dose level
Toxicologically significant compounds (animals, plants and environment)	Parent compound, IC-0, IM-2-1, IM-1-4 (no compound was considered relevant) Metabolite IM-1-5, stable in calcareous soils, is considered relevant
Metabolism in animals	Approximately > 90% metabolised. Mainly to the nicotinic acid derivative IC-O and demethylated compound IM-2-1 (approx. 50%) and IM-2-1, IS-1-1 and IS-2-1 (approx. 70%) in case of ring labeled and CN labeled, respectively (rats) Metabolite IM-1-5 (4.5%) is detected in rat metabolism only by HPLC analysis

Acute toxicity (Annex IIA, point 5.2)
Rat LD₅₀ oral	In water: 417 mg/kg b.w. (male) R22 314 mg/kg b.w. (female)
Rat LD₅₀ dermal	> 2000 mg/kg b.w.
Rat LC₅₀ inhalation	> 1.15 mg/l air
Skin irritation	Not irritant
Eye irritation	Not irritant

Skin sensitation

Not sensitizer (M&K)

Short term toxicity (Annex IIA, point 5.3)
Target / critical effect	Liver¹
Lowest relevant oral NOAEL / NOEL	12.4 mg/kg b.w./day (200 ppm), 90 day rat study
Lowest relevant dermal NOAEL	1000 mg/kg b.w./day, 21 day rabbit study
Lowest relevant inhalation NOAEL / NOEL	No data required

¹Increased relative liver weight, centrilobular hepatocellular hypertrophy)

Genotoxicity (Annex IIA, point 5.4)

Evidence of clastogenic potential in vitro. Τhis event was found to be not relevant for the in vivo situation with a negative mouse micronucleus assay and metaphase analysis in rat bone marrow²

² The genotoxic potential of acetamiprid was investigated in four in vitro studies (Ames test, mammalian cell gene mutation test in Chinese hamster ovary cells, mammalian cytogenetic test in Chinese hamster ovary cells, and mammalian cell DNA repair test in primary rat hepatocytes) and in three in vivo study (micronucleus test in mouse bone marrow, methapse analysis in rat bone marrow, and unscheduled DNA test in rat liver cells).

Long term toxicity and carcinogenicity (Annex IIA, point 5.5)
Target/critical effect	Liver and kidney³
Lowest relevant NOEL	7 mg/kg b.w./day (160 ppm), 2 year rat study
Carcinogenicity	No carcinogenic potential, treatment related mammary glands hyperplasia at 1000 ppm

³Liver: increased weight, pathology; kidney: increased weight

Reproductive toxicity (Annex IIA, point 5.6)
Reproduction target / critical effect	Reduced postnatal survival and decreased pup weight at parental toxic doses
Lowest relevant reproductive NOAEL / NOEL	6.5 mg/kg b.w./day (100 ppm) in rats⁴
Developmental target / critical effect	No teratogenicity or fetotoxicity was observed at the tested doses
Lowest relevant developmental NOAEL / NOEL	15 mg/kg b.w./day in rabbits⁵

⁴ this is the NOAEL parental, based on minimal transient effects on body weight and/or food consumption in the males from the next higher dose group during the growth phase. The NOAEL for pup development was 18 mg/kg b.w./day based on reduced postnatal survival. The NOEL for reproductive performance or fertility was 51 mg/kg b.w./day as no treatment related effects were observed over 2 generations.

⁵The NOAEL systemic adult toxicity:15 mg/kg b.w./day based on the inhibition of body weight gain and decrease in food consumption observed at 30 mg/kg b.w./day. There was no teratogenicity or fetotoxicity in fetuses even at 30 mg/kg b.w./day, the highest dose level employed.

Neurotoxicity / Delayed neurotoxicity (Annex IIA, point 5.7)

NOEL acute = 10 mg/kg b.w. based on reduced locomotor activity in the rat at high and medium dose

NOEL subchronic = 200 ppm (14.8 and 16.3 mg/kg b.w./day for males and females respectively) based on reduced body weight and food consumptions

Other toxicological studies (Annex IIA, point 5.8)

The metabolites IM-0, IM-1-3, IM-2-3 and IM-1-4 are considered harmful after single oral administration

The metabolite IM-1-5 is considered toxic after single oral administration

No evidence of genotoxicity in the Ames bacterial reverse mutation assay for IM-0, IM-1-2, IM-1-3, IM-2-1, IM-2-3, IS-1-1, IS-2-1, IC-0, IM-1-4, IM-1-5, IB-1-1 metabolites

Medical data (Annex IIA, point 5.9)

Currently limited: new active substance. No detrimental effects in manufacturing or development personnel

Summary (Annex IIA, point 5.10)	Value	Study	Safety factor
ADI	0.07 mg/kg b.w./day	2 year rat study and 2-generation rat reproductive study	100
AOEL short term AOEL long term	0.124 mg/kg b.w./day 0.07 mg/kg b.w./day	13-week rat study 2 year rat study and 2-generation rat reproductive study	100 100
ARfD (acute reference dose)	0.1 mg/kg b.w./day	Acute neurotoxicity rat study	100

Dermal absorption (Annex IIIA, point 7.3)

33.7% and 15.9% supported by in vivo dermal penetration data in rat for the diluted and the concentrated formulation EXP-80667A, respectively⁶

⁶See paragraph 4.2

Local effects

Acetamiprid does not produce local effects, neither after a single nor repeated exposure.

Data requirements active substance

No additional data requirements are identified.

4.1 Toxicity of the formulated product (IIIA 7.1)

The formulation Gazelle needs to be classified as R22 ‘Harmful if swallowed’, based on the acute oral toxicity (LD₅₀ rat 1065 mg/kg bw).

The formulation Gazelle does not need to be classified on the basis of its acute dermal (LD₅₀ rat > 2000 mg/kg bw), and inhalation toxicology (LC₅₀ rat >3500 mg/ m³).

The formulation Gazelle is not classifiable as a skin or eye irritant.

The formulation Gazelle does not have sensitising properties in a Buehler test.

4.1.1 Data requirements formulated product

No additional data requirements are identified.

4.2 Dermal absorption (IIIA 7.3)

See List of Endpoints. The in vivo dermal absorption study was performed with the formulation Gazelle as an SP (water soluble powder) formulation. The formulation has been changed into a SG (water soluble granule) formulation. The dermal absorption value from the SP formulation is considered applicable for the SG formulation.

4.3 Available toxicological data relating to non-active substances (IIIA 7.4)

The available toxicological data relating to non-active substances will be taken into account in the classification and labelling of the formulated product.

4.4 Exposure/risk assessments

The intended uses are listed in Appendix 1 (GAP).

4.4.1 Operator exposure/risk

According to the Dutch Plant Protection Products and Biocides Regulations the risk assessment is performed according to a tiered approach. There are four possible tiers:

Tier 1: Risk assessment using the EU-AOEL without the use of PPE

Tier 2: Risk assessment using the NL-AOEL without the use of PPE

Tier 3: Refinement of the risk assessment using new dermal absorption data

Tier 4: Prescription of PPE

Tier 1

Calculation of the EU-AOEL / Tolerable Limit Value (TLV)

For acetamiprid no TLV has been set. The AOEL will be used for the risk assessment.

The formulation Gazelle is applied by mechanical downward spraying in the production of flower bulbs, flower tubers and bulb flowers and applied by manual up and downward spraying in the production of flower bulbs, flower tubers and bulb flowers (indoor).

In the EU AOELs for short term and long term are derived. Considering the intended uses, mode of action of acetamiprid, and the kinetics of acetamiprid, an AOEL short term can be used for risk assessment for the operator.

The AOEL short term can also be used in the risk assessment for the worker. The compound is a systemically acting fungicide and is taken up by the plant. This combined with the fast excretion of acetamiprid in mammals justifies the use of the AOEL short term for the risk assessment for the worker.

Since acetamiprid is included in Annex I of 91/414/EEC, the semi-chronic EU-AOEL of 0.124 mg/kg bw/day (= 8.7 mg/day for a 70-kg operator), based on the 90 day study in rat is applied (see List of Endpoints).

Exposure/risk

Exposure to acetamiprid during mixing and loading and application of Gazelle is estimated with models. The exposure is estimated for the unprotected operator. In general, mixing and loading and application is performed by the same person. Therefore, for the total exposure, the respiratory and dermal exposure during mixing/loading and application have to be combined.

In the Table below the estimated internal exposure is compared with the systemic EU-AOEL.

Table T.1 Internal operator exposure to acetamiprid and risk assessment for the use of Gazelle

	Route	Estimated internal exposure ^a(mg /day)	Systemic EU-AOEL (mg/day)	Risk-index ^b
Mechanical downward spraying on flower bulbs (production), flower tubers and bulb flowers (uncovered)
Mixing/ Loading^c	Respiratory	0.03	8.7	<0.01
Mixing/ Loading^c	Dermal	0.64	8.7	0.07
Application^d	Respiratory	<0.01	8.7	<0.01
Application^d	Dermal	0.47	8.7	0.05
	Total	1.14	8.7	0.12
Manual up- and downward spraying on flower bulbs (production), flower tubers and bulb flowers (indoor)
Mixing/ Loading & application^e	Respiratory	0.05	8.7	0.01
Mixing/ Loading & application^e	Dermal	3.37	8.7	0.39
	Total	3.42	8.7	0.40

a Internal exposure was calculated with:

· biological availability via the dermal route: 15.9% (concentrate) and 33.7% (spray dilution) (see 4.2)

· biological availability via the respiratory route: 100% (worst case)

b The risk-index is calculated by dividing the internal exposure by the systemic AOEL.

c External exposure is estimated with NL-model.

d External exposure is estimated with EUROPOEM.

e External exposure is estimated with Dutch greenhouse model.

Since the EU-AOEL is not exceeded without the use of PPE, a higher tier assessment is not required.

4.4.2 Bystander exposure/risk

Field applications:

The bystander exposure is only a fraction of the operator exposure. Based on the low risk-index for the operator, no exposure calculations are performed for bystanders.

Greenhouse applications:

During spraying operations there should be no bystanders present in the greenhouse. No exposure to bystanders is therefore expected.

4.4.3 Worker exposure/risk

Shortly after application it is possible to perform re-entry activities during which intensive contact with the treated crop will occur (for both field and greenhouse application). Therefore, worker exposure is calculated.

The exposure is estimated for the unprotected worker. In Table T.2 the estimated internal exposure is compared with the systemic EU-AOEL. The exposure to the worker in the greenhouse is considered worst-case for the field application.

Table T. 2 Internal worker exposure to acetamiprid and risk assessment after application of Gazelle

	Route	Estimated internal exposure ^a(mg /day)	Systemic EU-AOEL (mg/day)	Risk-index ^b
Re-entry activities in the production of flower bulbs, flower tubers, and bulb flowers
	Respiratory	0.02	8.7	<0.01
	Dermal	1.52	8.7	0.17
	Total	1.54	8.7	0.17

a External exposure was estimated with [Dutch greenhouse model/ EUROPOEM II]. Internal exposure was calculated with:

· biological availability via the dermal route: 33.7% (see 4.2)

· biological availability via the respiratory route: 100% (worst case)

b The risk-index is calculated by dividing the internal exposure by the systemic AOEL.

Since the NL-AOEL is not exceeded without the use of PPE, a higher tier assessment is not required.

4.4.4 Re-entry

See 4.4.3 Worker exposure/risk.

Overall conclusion of the exposure/risk assessments of operator, bystander, and worker

The product complies with the Uniform Principles.

Operator exposure

Based on the risk assessment, it can be concluded that no adverse health effects are expected for the unprotected operator after dermal and respiratory exposure to acetamiprid as a result of the application of Gazelle in the production of flower bulbs, flower tubers, and bulb flowers.

Bystander exposure

Based on the risk assessment, it can be concluded that no adverse health effects are expected for the unprotected bystander due to exposure to acetamiprid during application of Gazelle in the production of flower bulbs, flower tubers, and bulb flowers.

Worker exposure

Based on the risk assessment, it can be concluded that no adverse health effects are expected for the unprotected worker after dermal and respiratory exposure during re-entry activities in the production of flower bulbs, flower tubers, and bulb flowers due to exposure to acetamiprid after application of Gazelle.

4.5 Appropriate mammalian toxicology and operator exposure endpoints relating to
the product and approved uses

See List of Endpoints.

4.6 Data requirements

None.

4.7 Combination toxicology

Gazelle contains only one active substance and it is not described that it should be used in combination with other formulations.

4.8 Mammalian toxicology classification and labelling

Proposal for the classification of the active ingredient (symbols and R phrases)
(EU classification)

Symbol:

Indication of danger: Harmful

Risk phrases

R22

Harmful if swallowed

Proposal for the classification and labelling of the formulation concerning health

The current classification and labelling, which is prepared in conformity with Directive 1999/45/EC, can be maintained.

Substances, present in the formulation, which should be mentioned on the label by their chemical name (other very toxic, toxic, corrosive or harmful substances):
-
Symbol:	Xn	Indication of danger:	Harmful
R phrases	R22	Harmful if swallowed.

S phrases	S22 S36/37 S46	Do not breathe dust. Wear suitable protective clothing and gloves. If swallowed, seek medical advice immediately and show this container or label.

Special provisions: DPD-phrases	-	-
Plant protection products phrase: DPD-phrase	DPD01	To avoid risk for man and the environment, comply with the instructions for use
Child-resistant fastening obligatory?			n/a
Tactile warning of danger obligatory?			n/a

5. Residues

Flower bulbs, flower tubers and bulb flowers are not for human consumption. The intended uses should be assessed for the risk for consumers with respect to the possible residues of acetamiprid or its metabolites in succeeding crops only.

In the field in the Netherlands, flower bulbs, flower tubers and bulb flowers can be followed by consumable crops. In the greenhouse 6 applications per year is expected not to lead to extra risks since degradation kinetics of soil residues is expected to be faster compared to the field situation. Furthermore, flower bulbs, flower tubers and bulb flowers grown in greenhouses are not expected to be followed by consumable crops.

The worst case situation which will be evaluated here is 3 applications of 46 g ai/ha per year in field grown flower bulbs, flower tubers and bulb flowers.

5.1.6 Residues in succeeding crops

A DT50, lab of 0.8- 5.4 d was found for the parent compound acetamiprid, corresponding to a DT90 value of less than 20d. This is below the trigger value of 100d. Acetamiprid parent is not expected to accumulate in succeeding crops and no rotational crop studies are required.

Acetamiprid is included in Annex I of Directive 91/414/EEC by Directive 2004/99/EC (into force: January 1^st, 2005). According to the warnings and precautions described in Annex I and II of the review report on acetamiprid, Member States should pay special attention to soil metabolite IM-1-5, since it might be present in high levels in soil. In the final version of the evaluation table (rev. 5-1, March 2004), metabolite IM-1-5 is considered a major metabolite in calcareous soils and also a toxicological relevant metabolite.

IM-1-5 is not part of rat metabolism, and it’s toxicology is not covered by the ADI and ARfD of acetamiprid. Metabolite IM-1-5 is considered toxic after single oral administration (see List of Endpoints of section 4. Toxicology and Metabolism). IM-1-5 is not suspected to be mutagenic (Amestest).

From the Draft Assessment Report (March 2001) and the addendum to the draft assessment report (January 2004) it was concluded that IM-1-5 is a major metabolite in soils with pH > 7.4. The metabolite was not found at pH ≤ 7.4 but was found at maximally 20% TRR at pH 7.7-8.0. DT50, lab of IM-1-5 is about 1y in silty clay loams and clay loam soils. These results were taken up in the List of endpoints at the time of Annex I inclusion.

The worst case scenario is of flower bulbs with a % crop cover of 20. The worst case scenario is 3 applications of 46 g ai/ha and 3 x 46 x 0.80 = 108 g /ha IM-1-5 reaches the soil surface. Aging does not play an important role since the DT50 value is long. Maximally 20% of the applied parent would be recovered as IM 1-5 corresponding to 21.6 g/ha. After harvest of the treated crops and ploughing the soil for 20 cm, the residue of IM 1-5 might be present in a level of 0.0065 mg/kg soil. This is an overestimation since a worst case crop cover % and a worst case DT50 (lab) were used.

The applicant submitted a calculation on uptake of IM 1-5 by plants. The uptake factor was estimated using a methodology also used by INS method (see 6.6.1 MTR). It assumes that uptake takes place with the water stream through the xylem, and that uptake is higher when the molecule is more water soluble. A comparison was made for acetamiprid, IM 1-4 and IM 1-5 using available Kow values, experimental uptake data and calculated uptake values. Available data strongly suggest that the plant uptake factor is < 1 for IM-1-5.

	acetamiprid	IM-1-4	IM-1-5
Log Kow	0.8	0.81	1.96
Experimental uptake factor	0.7	0.24	Not measured
Modellated uptake factor	0.28-2.14	0.28-2.14	0.42

Using a plant uptake factor of < 1, residue levels of ≤ 0.0065 mg/kg IM-1-5 will be present in succeeding crops. Since this is below the trigger value of 0.01 mg/kg and the metabolite is negative in an Ames test, no risk is expected for the consumer and no further toxicology data are required. IM-1-5 has not to be included in the residue definition and MRLs need not to be set.

The assessment of the use on flower bulbs, flower tubers and bulb flowers (20% crop interception) is worst case for the assessment of the use on potatoes (50% crop interception).

Conclusion

No risk is expected for consumers after consumption of succeeding crops cultivated after the flower bulbs, flower tubers and bulb flowers treated according to the intended use of Gazelle.

6. Environmental fate and behaviour

The Plant Protection Products and Biocides Regulations (RGB) published in the Government Gazette (Staatscourant) 188 of 28 September 2007 came into effect on 17 Oktober 2007, while repealing the Uniform Principles Decree on Plant Protection Products (BUBG) and the Regulation elaborating the uniform principles for plant protection products (RUUBG).

Risk assessment is done in accordance with Chapter 2 of the RGB for products based on
- active substances which have already been included in Annex I of directive 91/414/EEC

- “new” active substances;

Risk assessment is done in accordance with Chapter 10 of the RGB for products based on
- active substances which have not been included in Annex I of directive 91/414/EEC.

This means that for the current application of Gazelle, risk assessment is done in accordance with Chapter 2 of the RGB.

Acetamiprid is a new active substance, placed on Annex I. For the risk assessment the most recent List of Endpoints (final review report, 2004) is used.

Additional data were submitted to the Ctgb for former applications of Gazelle. These data are included in italics below the LoEP

List of Endpoints Fate/behaviour

Fate and behaviour in soil

Route of degradation
Aerobic:
Mineralisation after 100 days:	9.6 % 120 d
Non-extractable residues after 100 days:	32.3 % 120 d
Major metabolites above 10 % of applied active substance: name and/or code % of applied rate (range and maximum)	IM-1-4: 0.91 – 36.17% (day 0.25 - day 182), 53.9% (maximum, day 14 d)
Calcareous soils Major metabolites above 10 % of applied active substance: name and/or code % of applied rate (range and maximum)	IM-1-4: 1.95 – 0.86 % (day 0.25 - day 187), 21.15% (maximum, day 7)- sandy loam soil IM-1-5: 1.41 – 13.43 % (day 1 - day 182), 20.02 % (maximum, day 13) –silty clay loam soil IM-1-5: 0.83 – 8.29 % (day 0.25 - day 187), 12.89 % (maximum, day 7) –clay loam soil IM-1-2: 11.89 – 0.77 % (day 0.25 – day 28) 36.02 % (maximum, day 1) - sandy loam soil IC-0: 3.49 – 0.71% (day 3 – day 28) 10.23 % (maximum, day 7) - clay loam soil
Supplemental studies
Anaerobic:	Mineralisation 0.25 % (max. day 182) Non-extractable residues: 12.13 % (max., day 14) Major Metabolite: IM-1-4 46.7% (max. day 119 d)
Soil photolysis:	Mineralisation < 1 % Non-extractable residues 13 % (max., 30 d) Major Metabolite IM-1-4: 46.5 % (max. day 30 d irradiated samples) 65.3 % (max. day 30 dark control samples)
Remarks:	None

Rate of degradation
Laboratory studies
DT₅₀lab (20 °C, aerobic):	parent: 0.8- 5.4 d (n= 4, r² = 0.993- 0.997) mean 2.6 days; from DAR 0.8, 7.7, 1.3, 2.7, 5.4, 1.4 days geomean 2.3 (n=6) IM-1-4: 4.1-226.5 d (n= 3, r² = 0.872-0.997) Mean 133 days; from DAR: 23.7, 226.5, 168.5, 4.1, 33.6, 32.1 days, geomean 58.4 days (n=6)
DT₉₀lab (20 °C, aerobic):	Parent: DT₉₀lab: 2.8 – 67.3 d (n= 4, r² = 0.993- 0.997) mean 20.9 days IM-1-4: no data
DT₅₀lab (10 °C, aerobic):	7.7 d (n= 1, r² =0.997)
DT₅₀lab (20 °C, anaerobic):	71 d, total system (water and soil) (n= 1, r²= 0.99)
Calcareous soils DT₅₀lab (20 °C, aerobic):	Parent: mean 1.1 days (n=3, r²= 0.988-0.989) IM-1-5: > 365 days (r²= 0.969-0.986) (realistic worst-case DT₅₀’s : 450 days (silty clay loam soil), 388 days (clay loam soil ) (n=2) IM-1-2: 1.1-1.6 days (n=3, r²= 0.983-0.986), mean 1.3 days IM-1-4: 2.7 – 5.6 days (n=3, r²= 0.970-0.988), mean 3.9 days
Field studies (country or region)
DT_50f from soil dissipation studies:	parent DT_50f: Italy, cropped: 0.4 d (n= 1, r²=0.881) UK, cropped: 5.4 d (n= 1, r²=0.892) France, cropped: 4.1 d (n=1, r²=0.821) Spain, cropped: 1.6 d (n= 1, r²=0.851) Mean: 2.9 days DT₅₀ (IM-1-4): Italy: 17.1 d (n= 1, r²=1.0) UK: 50.1 d (n= 1, r²=0.901) France: 42.9 d (n=1, r²=0.907) Spain: 15.1 d (n= 1, r²=1.0) Mean: 31.3 days
DT_90f from soil dissipation studies:	parent DT_90f: Italy: 18.4 d; UK: 19.9 d; France: 31.2 d; Spain: 11.3 d Mean: 20.2 days DT₉₀ (IM-1-4): Italy: 56.7 d; UK: 166.5 d; France: 142.7 d; Spain: 50.2 d Mean: 104 days
Soil accumulation studies:	Not required
Soil residue studies:	Not relevant
Remarks: e.g. effect of soil pH on degradation rate	None

Adsorption/desorption
K_f / K_oc: K_d: pH dependence:	K_oc (parent): 71.1-138.4 (mean of 5 soils 106.5), ¹/_n= 0.825-0.907, (mean: 0.86) K_oc IM-1-4: 132-223 (mean of 4 soils: 171), ¹/_n= 0.712-0.816 (mean: 0.76) K_oc IC-0: 70-258 (mean of 5 soils: 122), ¹/_n= 0.894-1.007, (mean: 0.953) K_f (parent): 0.6-3.13 (mean of 5 soils 1.58), K_f IM-1-4: 2.16-5.79 (mean of 4 soils: 3. 22), K_f IC-0: 0.569-1.027 (mean of 5 soils 0. 752), Calcareous soils K_oc IM-1-2: 19 – 95 (mean of 4 soils: 54), ¹/_n= 0.856- 0.944 (mean: 0.903) K_f IM-1-2: 0.16- 3.60 (mean of 4 soils: 1.12) K_oc IM-1-5: 453 –563 (mean of 2 soils: 508) method of calculation: GH Bolt equation A new adsorption/desorption study for IM-1-5 is not considered necessary anymore. More information is included in the Evaluation Table. No dependence for parent. No dependence for the metabolites

Mobility
Laboratory studies:
Column leaching:	no data provided not required.
Aged residue leaching:	Guideline: BBA Test Guideline Teil IV, 4-2 Aged for (d): 2 d Time period (d): 4 d Precipitation (mm): 100 mm Leachate: 0.3-1.3% total radioactivity in leachate Leachate: 0.06% acetamiprid, 0.84% IM-1-4 88.9- 93.7% total radioactivity retained by the soil (the majority of radioactivity was detected in the four upper soil layers) Calcareous soils Two soils : EU sandy loam (pH: 8.4), US sandy loam (pH: 8.7) Aged for (d) : 64 d Leaching period: 20 d Precipitation (cm ) : 50.8 cm (equivalent to 1038 ml) Major metabolites during aging period: IC-0 : 33.5% (day 28) IM-1-2 : 27.3% (day 7) IM-1-4 : 11.7% (day 14) IM-1-5 : 8.8% (day 64) Mean DT₅₀ values Parent : 2.7 days, IM-1-2: 2.4 days IM-1-4 : 11.9 d, IC-0 : 33.7 d, IM-1-5: 122 d Leaching phase EU soil , Segment 1: 0-6 cm total 4.5% of A.R.( 3.9% associated with IM-1-5) EU soil , Segment 2 : 6-12 cm Total 1.7% of A.R.( mostly associated with IM-1-5) US soil , Segment 1: 0-6 cm total 5.3% of A.R.( 1.9% associated with IM-1-5) No significant quantities of radioactivity found in subsequent segments. Leachate EU soil : total 5% of A.R. (associated with IC-0) US soil : total 19.3% of A.R. (associated with IC-0)
Field studies:
Lysimeter/Field leaching studies:	no data submitted and no data required.
Remarks:	None

Fate and behaviour in water

Abiotic degradation
Hydrolytic degradation:	parent: stable at pHs 4, 5 and 7 at temperatures 22, 35 and 45°C
	pH9 (25°C) DT₅₀ : 420 days (calculated from Arrhenius plot) pH9 (35°C) DT₅₀ : 52.9 days pH9 (45°C) DT₅₀ : 13 days

Major metabolites:	pH9: 45°C IM-1-4: 14.8% AR (35 d) IM-1-3: 60.5% AR (35 d) IM-1-5: pH4 (20°C) DT₅₀: 67.2 d pH7 (20°C) DT₅₀: 159.2 d pH9 (20°C) DT₅₀: 23.5 d pH11 (20°C) DT₅₀: 19 hr
Photolytic degradation:	parent DT₅₀: 34 days (irratiated samples) no photodegradation in dark samples
Major metabolites:	IB-1-1: 35%AR (30 d) IC-0, DT₅₀: 0.4 days Florida summer sunlight IM-1-4: very low photolytic degradation rate IM-1-5 DT₅₀: 21.1 – 36.1 d (irradiated samples) Mean: 26.1 d DT₅₀: 36.2 – 152 d (dark control samples) Mean: 82.6 d

Biological degradation
Readily biodegradable:	Not readily biodegradable
Water/sediment study: DT₅₀ water: DT₉₀ water: DT₅₀ whole system: DT₉₀ whole system: Distribution in water / sediment systems (active substance) Distribution in water / sediment systems (metabolites)	Parent - DT₅₀ water: 3.6 – 5.8 days Parent – DT₉₀ water: 31.1 – 36.6 days (Biphasic kinetics, r²= 0.91-0.93, n= 2) IM-1-4, DT₅₀ water: 27.8 days (1^st order kinetics, r²= 0.89, n= 1) IC-0, DT₅₀ water: 84.5 days (1^st order kinetics, r²= 0.97, n= 1) Parent - DT₅₀ sediment: 40.1 – 44.4 days Mean: 42.3 d (Biphasic kinetics, r²= 0.90-0.99, n= 2) not calculated parent: 29.96% in water, 39% in sediment on day14 (1^st system- Manningtree) 19% in water, 36.55% in sediment on day 30 (2^nd system- Ongar) IM-1-4: max. 12.3% in water, 30.7% in sediment on day 30 (1^st system) max. 9.6% in water, 2.5% in sediment on day 14 (2^nd system) IC-0: max 26.15% in water, 3.32% in sediment on day 62 ( 2^nd system)
Accumulation in water and/or sediment:	Not relevant

Degradation in the saturated zone	no data provided, not required.
Remarks:	None

Fate and behaviour in air

Volatility
Vapour pressure:	1.73x10^-7 Pa at 50 ^oC (>99%). Expected <1x10^-6 Pa at 25 ^oC
Henry's law constant:	<5.3x10^-8 Pa m³ mol^-1at 25 ^oC

Photolytic degradation
Direct photolysis in air:	Not studied - no data requested
Photochemical oxidative degradation in air DT₅₀:	DT₅₀ of 0.140 days (Atkinson’s method)
Volatilisation:	from plant surfaces (BBA guideline): <1 % after 24 hours from soil (BBA guideline): <1% after 24 hours
Remarks:	None

New data

A normalisation of field studies was submitted by the applicant. The normalization procedure was summarized and evaluated by the CTB (12/2007)

Field DT₅₀ values for IM-1-4 were normalised for temperature and moisture according to FOCUS procedures and PECgw calculations were performed according to the Dutch procedures.

Data:

A field soil dissipation study in Europe performed at 4 locations with acetamiprid is available (Wicks, 1999). This study has been evaluated by the authorities (EU and NL) and the results were included in the List of Endpoints. In the Dutch evaluation of March 2006 it was stated that these studies apparently fulfilled the criteria for field dissipation studies, making them in principle suitable for the calculation of field degradation rates. This statement was accepted as such and was not further evaluated again.

Procedures:

Normalisation was performed following the “time-step normalisation” procedure outlined in Guidance Document on Estimating Persistence and Degradation Kinetics FOCUS (2005). The normalisation procedure used involves one of the possible options: reducing or increasing day lengths depending on soil temperature and moisture.

The factor for temperature correction is:

f_Temp = Q₁₀^(Ta-Tref)/10

with Q₁₀ = 2.2 (this is the most appropriate value based on available data)

Ta = actual soil temperature

Tref = reference soil temperature (20°C)

The factor for moisture correction is:

f_Moisture = (θa/θr)^0.7 (if θa≥θr then f_Moisture = 1)

with θa = actual moisture

θr = reference moisture (= moisture at 100% field capacity)

Because no actual soil moisture contents were available, the soils were assumed to be at or above field capacity (f_Moisture = 1). This will result in worst-case half-lives.

The normalised day length = D x f_Moisture x f_Temp

with D = 1 d

Cumulative corrected day lengths are calculated between each sampling interval to result in normalised days after application.

Half-lives of IM-1-4 were calculated for each site based on SFO kinetics, starting from the maximum amount of IM-1-4 and making use of the normalised days after application. Calculations were performed with ModelMaker vs 4.0 software.

Normalised field half-lives for the degradation of IM-1-4 in soil were

Bologna: 23.05 d; T correction factor in the range 0.92-1.53

Manningtree: 38.38 d; T correction factor in the range 0.30-1.01

Mereville: 43.83 d; T correction factor in the range 0.67-1.41

Sevilla: 28.67 d; T correction factor in the range 1.09-2.52

In principle the Sevilla site is not representative for NL because of the high temperatures resulting in the high T correction factor. This is also beyond the Q10 value range.

The geomean without this value would lead to a value of 33.8 d.

Because of the small differences the calculations with a geometric mean 32.5 d can be used in PEARL/GeoPEARL calculations.

Appendix A: Metabolite names, codes and other relevant information of the pesticide Gazelle with a.s. acetamiprid.

The compounds shown below were found in one or more studies involving the metabolism and/or environmental fate of acetamiprid. The parent compound structure of acetamiprid

is shown first in this list and followed by degradate or related compounds.

Compound name	Code number(s)	IUPAC name	Structural formula	Structure	Molecular Weight [g/mol]	Observed in study (% of occurrence/ formation)
acetamiprid	135410-20-7	(E)-N1-[(6-chloro-3-pyridyl)methyl]-N2-cyano-N1- methylacetamidine	C10H11ClN4		222.68
IM-1-4	amine				156.6	53.4% in soil; 12.3% in water/sed.
IM-1-5					-	20% in soil pH>8
IM-1-2	N-acetyl urea				-	36% in soil pH>8
IC-0	Carboxylic acid				157.6	10% in soil pH>8; 26.2% in water/sed.
IB-1-1					-	35% aquatic photolysis

6.1 Fate and behaviour in soil

6.1.1 Persistence in soil

Article 2.8 of the Plant Protection Products and Biocides Regulations (RGB) describes the authorisation criterion persistence. If for the evaluation of the product a higher tier risk assessment is necessary, a standard is to be set according to the MPC-INS^{^[1]} method. Currently this method equals the method described in the Technical Guidance Document (TGD). Additional guidance is presented in RIVM^{^[2]}-report 601782001/2007^{^[3]}.

For the current application this means the following:

Acetamiprid

The following laboratory DT₅₀ values are available for the active substance acetamiprid: 1.4, 5.4, 2.7, 0.8, 7.7, 1.3 days (geomean 2.3 days). The mean DT₅₀-value of the a.s. can thus be established to be <90 days. Furthermore it can be excluded that after 100 days there will be more than 70% of the initial dose present as bound (non-extractable) residues together with the formation of less than 5% of the initial dose as CO₂.

In this way, the standards for persistence as laid down in the RGB are met.

For the metabolite IM-1-4 the following DT₅₀-values are available: 23.7, 226.5, 168.5, 4.1, 333.6, 32.1 days (geomean 58.4 days ). Four field studies with this metabolite are available, of which two (UK and Northern France) are considered relevant for the Dutch situation. The DT₅₀ in these studies were 50.1 and 42.9 days. Based on these data, it can be concluded that the DT50 < 90 days.

Based on the above, the standards of persistence are met.

In the List of Endpoints some metabolites are mentioned which were formed on calcareous soils (pH > 8). Although in the Netherlands some calcareous soils are present, the pH in agricultural soils is < 8 (See also C 167.3.13). Therefore these metabolites are not further assessed.

PECsoil

The concentration of the a.s. acetamiprid and metabolite IM-1-4 in soil is needed to assess the risk for soil organisms (earthworms, micro-organisms). The PECsoil is calculated for the upper 5 cm of soil using a soil bulk density of 1500 kg/m³.

The following input data are used for the calculation:

PEC soil:

Active substance acetamiprid:

Maximum lab/field DT₅₀ for degradation in soil: 7.7 days

Molecular mass: 222.68 g/mol

Metabolite IM-1-4:

Maximum DT₅₀ for degradation in soil (20°C): 50.1days

Molecular mass: 156.6 g/mol

Correction factor: 53.9 (maximum observed percentage) * 0.70 (relative molar ratio = M metabolite/M parent) = 0.377

See Table M.1 for other input values and results.

PECsoil₂₁days is not relevant, because the log Pow < 3.

Table M.1 PECsoil calculations (5 cm (and 20 cm))

Use

Substance

Correction factor

Rate

[kg a.s./ha]

Freq.

Fraction on soil *

PIECsoil

5 cm

[mg a.s./kg]

Flowerbulbs, flower tubers, bulbflowers (F)

Acetamiprid

IM-1-4

0.377

0.046

0.017

0.8

0.05

0.038

* fraction on soil is detemined as 1 – interception value; interception values derived from Table 1.6 in “generic guidance for FOCUS groundwater scenarios”. Default value for fraction to soil, no interception values available.

These exposure concentrations are examined against ecotoxicological threshold values in section 7.5.

6.1.2 Leaching to shallow groundwater

Article 2.9 of the Plant Protection Products and Biocides Regulations (RGB) describes the authorisation criterion leaching to groundwater.

The leaching potential of the active substance (and metabolites) is calculated in the first tier using Pearl 3.3.3 and the FOCUS Kremsmünster scenario. Input variables are the actual worst-case application rate [0.05 resp. 0.046 kg/ha], the crop [winter cereals as default] and an interception value appropriate to the crop of [default fraction on soil; 0.8]. First date of yearly application is May 25^th (default) and October 1^st for autumn application. For metabolites all available data concerning substance properties are regarded. Metabolite IM-1-4 is included in the calculations. No other metabolites occurred above > 10 % of AR, > 5 % of AR at two consecutive sample points or had an increasing tendency.

The following input data are used for the calculation:

PEARL:

Active substance acetamiprid:

Geometric mean DT₅₀ for degradation in soil (20°C): 2.3 days

Arithmetic mean K_om (pH-independent): 61.8 L/kg

Arithm. mean 1/n: 0.86

Saturated vapour pressure: <1x10^-6 Pa (extrapolated to 25 ^oC)

Solubility in water: 2.95 g/L (25 ºC)

Molecular mass: 222.68 g/mol

Metabolite IM-1-4:

Geometric mean DT₅₀ for degradation in soil (20°C): 32.5 days

Arithmetric mean K_om (pH-independent): 136.6 L/kg

Arithm. mean 1/n: 0.73

Maximum fraction of occurence: 0.539

Saturated vapour pressure: <1x10^-6 Pa (parent value)

Solubility in water: 2.95 g/L (parent value)

Molecular mass: 156.6 g/mol

Other parameters: standard settings of PEARL 3.3.3

The following concentrations are predicted for the a.s. acetamiprid and the metabolite IM-1-4 following the realistic worst case GAP, see Table M.2.

Table M.2 Leaching of a.s. acetamiprid and metabolite IM-1-4 as predicted by PEARL 3.3.3

Use	Substance	Rate substance [kg/ha]	Frequency	Interval [days]	Fraction Intercepted *	PEC groundwater [mg/L]
						spring	autumn
Flowerbulbs, flower tubers, bulbflowers (G)	Acetamiprid IM-1-4	0.05	6	7	0.2	<0.001 <0.001	<0.001 <0.001
Flowerbulbs, flower tubers, bulbflowers (F)	Acetamiprid IM-1-4	0.046	3	30	0.2	<0.001 <0.001	<0.001 <0.001

* interception values derived from Table 1.6 in “generic guidance for FOCUS groundwater scenarios”. A default fraction to soil of 0.8 is used as worst case corresponding to an interception value of 0.2.

Results of Pearl 3.3.3 using the Kremsmünster scenario are examined against the standard of 0.01 µg/L. This is the standard of 0.1 µg/L with an additional safety factor of 10 for vulnerable groundwater protection areas (NL-specific situation).

From Table M.2 it reads that the expected leaching based on the PEARL-model calculations for the a.s. acetamiprid and its metabolite IM-1-4 is smaller than 0.01 µg/L for all proposed applications. Hence, the applications meet the standards for leaching as laid down in the RGB.

Lysimeter/field leaching studies

No field leaching studies or lysimeter study are available

Monitoring data

There are no data available regarding the presence of the substance acetamiprid and metabolite IM-1-4 in groundwater.

Conclusions

The proposed applications of the product comply with the requirements laid down in the RGB concerning persistence and leaching in soil.

6.2 Fate and behaviour in water

6.2.1 Rate and route of degradation in surface water

The exposure concentrations of the active substance acetamiprid and metabolites IM-1-4 and IC-0 in surface water have been estimated for the various proposed uses using calculations of surface water concentrations (in a ditch of 30 cm depth), which originate from spray drift during application of the active substance. The spray drift percentage depends on the use. For glasshouse a value of 0.1% is used and for field use a value of 1%.

Concentrations in surface water are calculated using the model TOXSWA. The following input data are used for the calculation:

TOXSWA:

Active substance:

geometric mean DT₅₀ for degradation in water at 20°C: 24.8 days

DT₅₀ for degradation in sediment at 20°C: 1000 days (default).

Arithm. mean K_om for suspended organic matter: 61.8 L/kg

Arithm. mean K_om for sediment: 61.8 L/kg

Arithm. mean 1/n: 0.86

Saturated vapour pressure: <1 x 10^-6 Pa (extrapolated to 25 ºC)

Solubility in water: 2.95 g/L (25 ºC)

Molecular mass: 222.68 g/mol

Metabolite IM-1-4:

Mean DT₅₀ for degradation in water at 20°C: 127 days

DT₅₀ for degradation in sediment at 20°C: 1000 days (default).

Arithm. mean K_om for suspended organic matter: 136.6 L/kg

Arithm. mean K_om for sediment: 136.6 L/kg

Arithm. mean 1/n: 0.73

Saturated vapour pressure: <1 x 10^-6 Pa (parent value)

Solubility in water: 2.95 g/L (parent value)

Molecular mass: 156.6 g/mol

Correction factor: 12.3 (max. % observed) * 0.70 (relative molar ratio = M metabolite/ M parent) = 0.086

Metabolite IC-0:

Mean DT₅₀ for degradation in water at 20°C: 172 days

DT₅₀ for degradation in sediment at 20°C: 1000 days (default).

Arithm. mean K_om for suspended organic matter: 67.3 L/kg

Arithm. mean K_om for sediment: 67.3 L/kg

Arithm. mean 1/n: 0.939

Saturated vapour pressure: <1 x 10^-6 Pa (parent value)

Solubility in water: 2.95 g/L (parent value)

Molecular mass: 157.6 g/mol

Correction factor: 26.15 (max. % observed) * 0.71 (relative molar ratio = M metabolite/ M parent) = 0.185

Other parameters: standard settings TOXSWA

When no separate degradation half-lives (DegT50 values) are available for the water and sediment compartment (accepted level P-II values), the system degradation half-life (DegT50-system, level P-I) is used as input for the degrading compartment and a default value of 1000 days is to be used for the compartment in which no degradation is assumed. This is in line with the recommendations in the FOCUS Guidance Document on Degradation Kinetics.

For metabolites, the level M-I values are used (system DegT50 value) only, since level M-II criteria have not been fully developed under FOCUS Degradation Kinetics.

In Table M.3, the drift percentages and calculated surface water concentrations for the active substance acetamiprid and its metabolites IM-1-4 and IC-0 for each intended use are presented.

Metabolites are modelled in TOXSWA as parent substances with a correction for formation and relative molecular mass on the application rate.

Table M.3 Overview of surface water concentrations for active substance and metabolites following spring/autumn application in the edge-of-field ditch

Use	Substance	Rate a.s. [kg/ha]	Freq.	Inter-val	Drift [%]	PIEC [mg/L]^*		PEC21 [mg/L]^*		PEC28 [mg/L]^*
						Spring	autumn	spring	autumn	spring	autumn
Flowerbulbs, flower tubers, bulbflowers (G)	Acetamiprid IM-1-4 IC-0	0.05 0.004 0.0093	6	7	0.1	0.063 0.005 0.012	0.024 - -	0.050 0.004 0.011	0.0099 - -	0.047 0.004 0.010	0.0075 - -
Flowerbulbs, flower tubers,bulbflowers (F)	Acetamiprid IM-1-4 IC-0	0.046 0.004 0.0085	3	30	1	0.300 0.028 0.061	0.219 - -	0.197 0.019 0.041	0.031 - -	0.182 0.018 0.039	0.023 - -

^*calculated according to TOXSWA

The exposure concentrations in surface water are compared to the ecotoxicological threshold values in section 7.2.

Monitoring data

The Pesticide Atlas on internet (www.pesticidesatlas.nl, www.bestrijdingsmiddelenatlas.nl) is used to evaluate measured concentrations of pesticides in Dutch surface water, and to assess whether the observed concentrations exceed threshold values.

Dutch water boards have a well-established programme for monitoring pesticide contamination of surface waters. In the Pesticide Atlas, these monitoring data are processed into a graphic format accessible on-line and aiming to provide an insight into measured pesticide contamination of Dutch surface waters against environmental standards.

Recently, the new version 2.0 was released. This new version of the Pesticide Atlas does not contain the land use correlation analysis needed to draw relevant conclusions for the authorisation procedure. Instead a link to the land use analysis performed in version 1.0 is made, in which the analysis is made on the basis of data aggregation based on grid cells of either 5 x 5 km or 1 x 1 km.

Data from the Pesticide Atlas are used to evaluate potential exceeding of the authorisation threshold and the MPC (ad-hoc or according to INS) threshold.

For examination against the drinking water criterion, another database (VEWIN) is used, since the drinking water criterion is only examined at drinking water abstraction points. For the assessment of the proposed applications regarding the drinking water criterion, see next section.

acetamiprid

The active substance acetamiprid was observed in the surface water (most recent data from 2007). In Table M.4 the number of observations in the surface water are presented.

In the Pesticide Atlas, surface water concentrations are compared to the authorisation threshold value of 100 µg/L (27-2-2006, C-167.3.13, consisting of first or higher tier acute or chronic ecotoxicological threshold value, including relevant safety factors, which is used for risk assessment, in this case 0.1*EC50 lemna) and to the indicative Maximum Permissible Concentration (MPC) of 0.1 µg/L as presented in the Pesticide Atlas (data source for the MPC: Zoeksysteem normen voor het waterbeheer, http://www.helpdeskwater.nl/normen_zoeksysteem/normen.php).

Currently, this MPC value is not harmonised, which means that not all available ecotoxicological data for this substance are included in the threshold value. In the near future and in the framework of the Water Framework Directive, new quality criteria will be developed which will include both MPC data as well as authorisation data.

The currently available MPC value is reported here for information purposes. Pending this policy development (finalisation for all substances expected in 2009-2010), however, no consequences can be drawn for the proposed applications.

Table M.4 Monitoring data in Dutch surface water (from www.pesticidesatlas.nl, version 2.0)

Total no of locations

(2007)

n > authorisation threshold

n > indicative/ad hoc MPC threshold

n > MPC-INS threshold *

163**

n.a.

n.a.: no MPC-INS available. < : exceeding expected to be lower than with indicative/ad hoc MPC value; > : exceeding expected to be higher than with 4^th Document MPC value

** the number of observations at each location varies between 1 and 30, total number of measurements is 630 in 2007.

The correlation of exceedings with land use is derived from the 1.0 version of the Pesticide Atlas. Hence, the correlation is not based on the exact same monitoring data. However, this is the best available information and therefore it is used in this assessment.

As there is no exceeding observed this cannot be correlated to the proposed or already authorised uses.

Therefore, no consequences can be drawn from the observed concentrations.

Drinking water criterion

It follows from the decision of the Court of Appeal on Trade and Industry of 19 August 2005 (Awb 04/37 (General Administrative Law Act)) that when considering an application, the Ctgb should, on the basis of the scientific and technical knowledge and taking into account the data submitted with the application, also judge the application according to the drinking water criterion ‘surface water intended for drinking water production’. No mathematical model for this aspect is available. This means that any data that is available cannot be adequately taken into account. It is therefore not possible to arrive at a scientifically well-founded assessment according to this criterion. The Ctgb has not been given the instruments for testing surface water from which drinking water is produced according to the drinking water criterion. In order to comply with the Court’s decision, however - from which it can be concluded that the Ctgb should make an effort to give an opinion on this point – and as provisional measure, to avoid a situation where no authorisation at all can be granted during the development of a model generation of the data necessary, the Ctgb has investigated whether the product under consideration and the active substance could give cause for concern about the drinking water criterion.

Acetamiprid has been on the Dutch market for > 3 years (authorised since 24-03-2006). This period is sufficiently large to consider the market share to be established. From the general scientific knowledge collected by the Ctgb about the product and its active substance, the Ctgb concludes that there are in this case no concrete indications for concern about the consequences of this product for surface water from which drinking water is produced, when used in compliance with the directions for use. The Ctgb does under this approach expect no exceeding of the drinking water criterion. The standards for surface water destined for the production of drinking water as laid down in the RGB are met.

6.3 Fate and behaviour in air

Route and rate of degradation in air

acetamiprid

The vapour pressure is 1 x 10^-6 Pa at 25°C. The Henry constant is <5.3x10^-8 Pa m³ mol^-1 at 25 ºC. The half-life in air is 0.14 days (Atkinson calculation).

Since at present there is no framework to assess fate and behaviour in air of plant protection products, for the time being this issue is not taken into consideration.

6.4 Appropriate fate and behaviour endpoints relating to the product and approved uses

See List of Endpoints.

6.5 Data requirements

None.

6.6 Overall conclusions fate and behaviour

It can be concluded that:

the active substance acetamiprid meets the standards for persistence in soil as laid down in the RGB.
metabolite IM-1-4 meets the standards for persistence in soil as laid down in the RGB.
all proposed applications of the active substance acetamiprid meet the standards for leaching to the shallow groundwater as laid down in the RGB.
all proposed applications of metabolite IM-1-4 meet the standards for leaching to shallow groundwater as laid down in the RGB.
all proposed applications of the active substance acetamiprid meet the standards for surface water destined for the production of drinking water as laid down in the RGB.

7. Ecotoxicology

The Plant Protection Products and Biocides Regulations (RGB) published in the Government Gazette (Staatscourant) 188 of 28 September 2007 came into effect on 17 October 2007, while repealing the Uniform Principles Decree on Plant Protection Products (BUBG) and the Regulation elaborating the uniform principles for plant protection products (RUUBG).

Risk assessment is done in accordance with Chapter 2 of the RGB for products based on
- active substances which have already been placed on Annex I of directive 91/414/EEC

- “new” active substances

This means that for the current application of Gazelle, risk assessment is done in accordance with Chapter 2 of the RGB.

List of Endpoints Ecotoxicology

Acetamiprid is a new active substance, included in Annex I. For the risk assessment the most recent List of Endpoints (SANCO/1392/2001, Final review report, June 16 2004) is used. It is stated that Member States should pay particular attention to the protection of aquatic organisms.

In the DAR, the product EXP 60707 was evaluated, which is identical to Gazelle. EXP 60707A is the formulation imported from Japan. EXP 60707B is the same formulation which according to the Notifier will be produced in Europe with additives from the European market

List of Endpoints Ecotoxicology

Terrestrial Vertebrates

Acute toxicity to mammals:	LD₅₀ 213 mg/kg bw (rats)
Acute toxicity to birds:	LD₅₀ 98 mg/kg bw (mallard duck)
Dietary toxicity to birds:	LC₅₀ >5000 ppm (>741 mg/kg bw/d) (bobwhite quail)
Reproductive toxicity to birds:	NOEL 250 ppm (25.1 mg/kg bw/d) (mallard duck)
Short term oral toxicity to mammals:	NOEL= 15 mg/kg/d

Aquatic Organisms

	Species	Test substance	Time Scale	Toxicity (mg/L)	Endpoint
Acute toxicity fish:	Oncorhynchis mykiss	Acetamiprid	96 h	>100	Mortality, EC₅₀
Acute toxicity fish:	Oncorhynchis mykiss	Metabolite IM-1-4	96 h	98.1	Mortality, LC₅₀
Long term toxicity fish:	Pimephales promelas	Acetamiprid	35 days	19.2	Growth NOEC
Bioaccumulation fish:	Not relevant
Acute toxicity invertebrate:	Daphnia magna	Acetamiprid	48 h	49.8	Mortality, EC₅₀
	Daphnia magna	Metabolite IM-1-4	48 h	43.9	Mortality, EC₅₀
	Daphnia magna	Metabolite IM-1-2	48 h	99.8	Mortality, EC₅₀
	Daphnia magna	Metabolite IC-0	48 h	>95.1	Mortality, EC₅₀
	Daphnia magna	Metabolite IB-I-I (taken from DAR)	48 h	>100.8	Mortality, EC₅₀
	Daphnia magna	EXP 60707A (acetamiprid 20 %)	48 h	>159	Mortality, EC₅₀
Chronic toxicity invertebrate:	Daphnia magna	Acetamiprid	21 d	5	Reproduction, NOEC
Acute toxicity algae:	Scenedesmus subspicatus	Acetamiprid	72 h	>98.3	Biomass, EC₅₀
Acute toxicity algae:	Scenedesmus subspicatus	EXP 60707A (acetamiprid 20 %)	72 h	>97.8	Biomass, EC₅₀
Chronic toxicity sediment dwelling organism:	Chironomus riparius	Acetamiprid	28 days	0.005	Emergence & developmental rate, NOEC
Chronic toxicity sediment dwelling organism:	Chironomus riparius	Metabolite IM-1-4	48 h	76.0	Mortality, LC₅₀
Acute toxicity aquatic plants:	Lemna gibba	Acetamiprid	14 d	1.0	Fronds, EC₅₀
Acute toxicity STP:	Activated sludge	Acetamiprid	3 h	> 1000	EC₅₀

Honeybees

Acute oral toxicity:

LD 50 ~ 14.53 microg./bee (acetamiprid)

LD50 8.85 microg. a.s./bee (EXP 60707 A tested formulation) (acetamiprid 20 %)

Acute contact toxicity:

LD50 ~ 8.09 microg./bee (acetamiprid)

LD50 9.26 microg. a.s./bee (EXP 60707 A tested formulation) (acetamiprid 20 %)

Other arthropod species

Test species	Application³	Status (kg as/ha)	Endpoints	% adverse effect ⁴
Typhlodromus pyri	Protonymphs (exposure on glass plates)	0.09-0.18	Mortality Fertility	100 No eggs
Aphidius rhopalosiphi	Adult (exposure on glass plates)	0.2-0.4	Mortality Fertility	100 No fecundity
Coccinella septempunctata	3 days old larvae (exposure on glass plates)	0.09-0.18	Mortality Fertility	100 No fecundity
Poecilus cupreus	Adult (exposure on quartz sand)	0.2-0.4	Mortality Feeding rate	£ 3.3 0.17 (same as the control)
*Extended laboratory tests¹*
Typhlodromus pyri	Protonymphs (exposure on sprayed bean leaves)	0.01, 0.018, 0.032, 0.057, 0.1 (in 200 l/ha water)	Mortality Fertility	51.7 (at 0.018 Kg /ha) No effect on repro. up to 0.032 Kg /ha) LR50: 29.7 g a.s./ha
Aphidius rhopalosiphi	Adult (exposure on sprayed potted barley plants)	0.001, 0.003, 0.009, 0.027, 0.081 (in 200 l/ha water)	Mortality Fertility	53.1 (at 0.009 Kg /ha) No effect on repro. up to 0.009 Kg /ha) LR50: 9.7 g a.s./ha
*Extended laboratory tests²*
Typhlodromus pyri	Protonymphs (exposure on leaves from sprayed apple trees)	Off-crop (13 g a.s./ha) In-crop (100 g a.s./ha)	Corrected Mortality % Sublethal effects (% reduction) Corrected Mortality % Sublethal effects (% reduction)	- 1.1 (day 0) 6.2 (day 0) 39.1 (day 0) to 5.1 (day 14) Not assessed
Aphidius rhopalosiphi	Adult (exposure on leaves from sprayed apple trees)	Off-crop (13 g a.s./ha) In-crop (100 g a.s./ha)	Corrected Mortality % Sublethal effects (% reduction) Corrected Mortality % Sublethal effects (% reduction)	90 (day 0) to 0 (day 14) 42.4 (day 7) to 32.5 (day 21) 70 (day 0) to 0 (day 21) 54.7 (day 7) to 34.6 (day 21)
Coccinella septempunctata	3 days old larvae (exposure on leaves from sprayed apple trees)	Off-crop (13 g a.s./ha) In-crop (100 g a.s./ha)	Corrected Mortality % Sublethal effects (% reduction) Corrected Mortality % Sublethal effects (% reduction)	42.9 (day 0) to 4.3 (day 14) -16.4 (day 7) 95.9 (day 0) to26 (day 28) 14.4 (day 28)
Chrysoperla carnea	3 days old larvae (exposure on leaves from sprayed apple trees)	Off-crop (13 g a.s./ha) In-crop (100 g a.s./ha)	Corrected Mortality % Sublethal effects (% reduction) Corrected Mortality % Sublethal effects (% reduction)	2.3 (day 0) to –0.1 (day 14) 7.5 (day 7) 16.3 (day 0) to 6.5 (day 14) 14.9 (day 7)
¹ extended lab tests,see monograph ²extended lab tests with fresh and aged residues, see addendum ecotox October 2002. ³Test substance in all tests = ECP60707A (200 g acetamiprid/kg) = Gazelle ⁴ Adverse effect means: x % effect on mortality = x % increase of mortality compared to control y % effect on a sublethal parameter = y % decrease of sublethal paramether compared to control (sublethal parameters are e.g. reproduction, parasitism, food consumption) When effects are favourable for the test organisms, a + sign is used for the sublethal effect percentages (i.e. increase of e.g. reproduction) and a – sign for mortality effect percentages (i.e. decrease of mortality).

Earthworms

Acute toxicity:

9 mg/kg (at day 14 - acetamiprid)

18.3 mg/Kg (at day 14 - EXP 60707) = 3.66 g a.s./kg

> 1000 mg/Kg (at day 14 - metabolites IM-1-4 & IC-0)

> 1000 mg/Kg (at day 14 - metabolites IM-1-2)

> 1000 mg/Kg (at day 14 - metabolites IM-1-5)

Reproductive toxicity:

NOEC 1.26 mg/Kg (8 weeks - EXP 60707) = 0.252 mg a.s./kg

Soil micro-organisms

Nitrogen mineralization:	No statistically significant effects > ± 25% compared to control control when acetamiprid is applied at 0.2 Kg a.s./ha
Carbon mineralization:	No statistically significant effects > ± 25% compared to control control when acetamiprid is applied at 0.2 Kg a.s./ha

Activated sludge(taken from DAR)

EC50 > 1000 mg a.s./L

7.1 Effects on birds

For the field use, birds can be exposed to the active substance acetamiprid via natural food (sprayed insects, seeds, leafs), drinking water and as a result of secondary poisoning. For the glasshouse use, only exposure via drinking water and fish is relevant.

The threshold value for birds is based on the trigger from the RGB. This means that Toxicity-Exposure Ratio’s (TERs) for acute and short-term exposure should be ³ 10 and TER for chronic exposure should be ³ 5.

Table E.1 presents an overview of toxicity data.

Table E.1 Overview of toxicity data for birds for substance acetamiprid

	Endpoint	Value
Acute toxicity to birds:	LD₅₀	98 mg a.s./kg bw
Dietary toxicity to birds:	LC₅₀	>741 mg a.s./kg bw/d
Reproductive toxicity to birds:	NOEL	25.1 mg a.s./kg bw/d

7.1.1 Natural food and drinking water

Sprayed products

Procedures for risk assessment for birds comply with the recommendations in the Guidance Document on Risk Assessment for Birds and Mammals under Council Directive 91/414/EEC (Sanco/4145/2000).

For the current application, uses can be categorized as leafy crops. Depending on the crop category, different indicator species are chosen. Table E.2 shows which indicator species are relevant for which uses.

Table E.2 Indicator species per use

Use	Crop	Indicator species
flower bulbs, flower tubers and bulb flowers	leafy crops	medium herbivorous and insectivorous

Table E.3a-c show the TER values for birds. The estimated daily uptake values (ETE, Estimated Theoretical Exposure) for acute, short-term and long-term exposure are calculated using the Food Intake Rate of the indicator species (FIR) divided by the body weight of the indicator species (bw), the Residue per Unit Dose (RUD), a time-weighted-average factor (f_TWA, only for long term) and the application rate. For uses with frequency > 1, a MAF (Multiple Application Factor) may be applicable. The ETE is calculated as application rate * (FIR/bw) * RUD * MAF [* f_TWA, only for long term]. The ETE is compared to the relevant toxicity figure. TER should be above the trigger for an acceptable risk.

Table E.3a Acute risk for birds

Substance		FIR / bw	RUD	Applica-tion rate (kg a.s./ha)	MAF	Acute ETE	LD50 (mg/kg bw/d)	TER
Substance		FIR / bw	RUD	Applica-tion rate (kg a.s./ha)	MAF	(mg/kg bw/d)	LD50 (mg/kg bw/d)	(trigger 10)
medium herbivorous bird
acetamiprid		0.76	87	0.046	1.3*	4.0	98	25
	insectivorous bird
	acetamiprid	1.04	52	0.046	n.a.	2.5	98	39

* Worst case value, for interval 14 days (MAF for interval 30 days is not given in the guidance document).

Table E.3b Short-term risk for birds

Substance		FIR / bw	RUD	Applica-tion rate (kg a.s./ha)	MAF	Short-term ETE	LC50 (mg/kg bw/d)	TER
Substance		FIR / bw	RUD	Applica-tion rate (kg a.s./ha)	MAF	(mg/kg bw/d)	LC50 (mg/kg bw/d)	(trigger 10)
medium herbivorous bird
acetamiprid		0.76	40	0.046	1.14	1.6	>741	>465
	insectivorous bird
	acetamiprid	1.04	29	0.046	n.a.	1.4	>741	>534

Table E.3c Long-term risk for birds

Substance		FIR / bw	RUD	Applica-tion rate (kg a.s./ha)	MAF	ftwa	Long-term ETE	NOEL (mg/kg bw/d)	TER
Substance		FIR / bw	RUD	Applica-tion rate (kg a.s./ha)		ftwa	(mg/kg bw/d)	NOEL (mg/kg bw/d)	(trigger 5)
medium herbivorous bird
acetamiprid		0.76	40	0.046	1.14	0.53	0.84	25.1	30
	insectivorous bird
	acetamiprid	1.04	29	0.046	n.a.	n.a.	1.4	25.1	18

Taking the results in Table E.3 into account, it appears that all proposed uses meet the standards laid down in the RGB.

drinking water

The risk from exposure through drinking surface water is calculated for a small bird with body weight 10 g and a DWI (daily water intake) of 2.7 g/d. Surface water concentrations are calculated using TOXSWA (see paragraph 6.2.1). In the first instance, acute exposure is taken into account. The highest PIEC_wateris 0.300 mg/L. It follows that the risk of drinking water is (LD50 * bw) / (PIEC*DWI) = (98 * 0.010) / (0.000300 * 0.0027) = 1.2*10⁶. Since TER >> 10, the risk is acceptable.

7.1.2 Secondary poisoning

The risk as a result of secondary poisoning is assessed based on bioconcentration in fish and worms.

Since the log Kow of acetamiprid < 3 (0.8), the potential for bioaccumulation is considered low and no further assessment is deemed necessary. Also for metabolites IM-1-4 and IC-0 the Log Pow is < 3 (no exact value available). Metabolites IM-1-5 and IM-1-2 occur only in calcareous soils (pH > 8). Although in the Netherlands some calcareous soils are present, the pH in agricultural soils is < 8 (See also C 167.3.13). Therefore these metabolites are not further assessed. Aquatic photolysis metabolite IB-1-1 is not expected to have a logPow > 3 based on its structure. Therefore, the risk of bioaccumulation of the a.s. and its metabolites is low.

Conclusions birds

The product complies with the RGB.

7.2 Effects on aquatic organisms

7.2.1 Aquatic organisms

The risk for aquatic organisms is assessed by comparing toxicity values with surface water exposure concentrations from section 6.2. Risk assessment is based on toxicity-exposure ratio’s (TERs).

Toxicity data for aquatic organisms are presented in Table E.6 for the active substance acetamiprid and metabolites IM-1-4, IC-0 and IB-1-1. Also the effects on macrophytes (aquatic plants) are evaluated.

Table E.4 Overview toxicity endpoints for aquatic organisms

Substance	Organism	Lowest		Toxicity value
		L(E)C₅₀ [mg/L]	NOEC [mg/L]	[mg/L]
acetamiprid	Acute
	Algae	>98.3		>97800
	Daphnids	49.8		49800
	Fish	>100		>100000
	Macrophytes	1.0		1000
	Chronic
	Daphnids		5.0	5000
	Fish		19.2	19200
IM-1-4	Acute
	Daphnids	43.9		43900
	Fish	98.1		98100
IC-0	Acute
	Daphnids	>95.1		>95100
IB-I-I	Acute
	Daphnids	>100.8		>100800
EXP60707A, (original Japanese form of Gazelle)	Acute
	Algae	>97.8		>97800
	Daphnids	>159		>159000
	Fish	-

These toxicity values are compared to the surface water concentrations calculated in section 6.2. Trigger values for acute exposure are 100 for daphnids and fish (0.01 times the lowest L(E)C₅₀-value) and 10 for algae and macrophytes (0.1 times the lowest EC₅₀-value). Trigger values for chronic exposure are 10 for daphnids and fish (0.1 times the lowest NOEC-values).

For acute and chronic risk, the initial concentration is used (PIEC) for TER calculation.

In table E.5 TER values for aquatic organisms are shown for the worst-case use in the field.

Table E.5a TER values for active substance acetamiprid: acute

Use	Substance	PECsw [mg a.s./L]	TER_st (trigger 10)	TER_st (trigger 100)	TER_st (trigger 100)	TER_st (trigger 10)
			Algae	Daphnid	Fish	Macrophytes
			spring	spring	spring	spring
Production of flower bulbs, flower tubers and bulb flowers	acetamiprid	0.300	>10000	>10000	>10000	3333

Table E.5b TER values for active substance acetamiprid: chronic

Use	Substance	PECsw [mg a.s./L]	TER_lt (trigger 10)	TER_lt (trigger 10)
			Daphnid	Fish
			spring	Spring
Production of flower bulbs, flower tubers and bulb flowers	acetamiprid	0.300	>10000	>10000

Taking the results in Table E.5a and b into account, the acute TERs for fish and Daphnia magna are above the relevant Annex VI triggers of 100 and the acute TERs for algae and Lemna are above the relevant Annex VI triggers of 10. The chronic TERs for fish and Daphnia magna are above the relevant Annex VI triggers of 10. Thus, it appears that for the active substance acetamiprid the proposed uses meet the standards for aquatic organisms as laid down in the RGB.

Metabolites IM-1-4, IC-0 and IB-I-I have formation fractions of respectively 0.123, 0.262 and 0.35. Although these metabolites are more persistent in water it is not expected that the PIEC will exceed the PIEC concentration of acetamiprid (PIEC values calculated for IM-1-4 and IC-0 in section 6.2). Considering the low or comparable toxicity of the three metabolites the risk is covered in the risk assessment of the parent.

7.2.2 Risk assessment for bioconcentration

Since logKow of acetamiprid and its water metabolites is < 3 (see 7.1.2), experimental data are not required.

Therefore the active substance acetamiprid meets the standards for bioconcentration.

7.2.3 Risk assessment for sediment organisms

The NOEC value for Chironomus is 5 µg/L. When this value is examined against the worst-case PIEC in water of 0.300 µg/L, the TER value is 16.7 and the trigger value of 10 is exceeded. Therefore, the active substance acetamiprid meets the standards for sediment organisms.

The only metabolite which was found in >10% in the sediment is IM-1-4. For metabolite IM-1-4 a NOEC of 76 mg/L is available. Since the expected water concentration of this metabolite is lower than the parent and since the metabolite is less toxic than the parent, no risk is expected for this metabolite.

Conclusions aquatic organisms

The proposed applications meet the standards for aquatic organisms.

7.3 Effects on terrestrial vertebrates other than birds

For the field use, mammals can be exposed to the active substance acetamiprid via natural food (sprayed insects, seeds, leafs), drinking water and as a result of secondary poisoning. For the glasshouse use, only exposure via drinking water and fish is relevant.

The threshold value for mammals is based on the trigger from the RGB. This means that the Toxicity-Exposure Ratio (TER) for acute exposure should be ³ 10 and TER for chronic exposure should be ³ 5. Dietary toxicity is not taken into account for mammals.

Table E.6 presents an overview of toxicity data.

Table E.6 Overview of toxicity data for mammals

	Endpoint	Value
Acute toxicity to mammals:	LD₅₀	213 mg a.s./kg bw
Reproductive toxicity to mammals:	NOEL	15 mg a.s./kg bw/d

7.3.1 Natural food and drinking water

Sprayed products

Procedures for risk assessment for mammals comply with the recommendations in the Guidance Document on Risk Assessment for Birds and Mammals under Council Directive 91/414/EEC (Sanco/4145/2000).

For the current application, uses can be categorized as leafy crops. Depending on the crop category different indicator species are chosen. Table E.7 shows which indicator species are relevant for which uses.

Table E.7 Indicator species per use

Use	Crop	Indicator species
flower bulbs, flower tubers and bulb flowers	leafy crops	medium herbivorous

Table E.8a-b show the estimated daily uptake values (ETE, Estimated Theoretical Exposure) for acute and long-term exposure, using the Food Intake Rate of the indicator species (FIR) divided by the body weight of the indicator species (bw), the Residue per Unit Dose (RUD), a time-weighted-average factor (f_TWA, only for long term) and the application rate. For uses with frequency of > 1, a MAF (Multiple Application Factor) may be applicable. The ETE is calculated as application rate * (FIR/bw) * RUD * MAF [* f_TWA, only for long term]. The ETE is compared to the relevant toxicity figure. TER should be above the trigger for an acceptable risk.

Table E.8a Acute risk for mammals

Substance	FIR / bw	RUD	Applica-tion rate (kg a.s./ha)	MAF	Acute ETE	LD50 (mg/kg bw/d)	TER
Substance	FIR / bw	RUD	Applica-tion rate (kg a.s./ha)	MAF	(mg/kg bw/d)	LD50 (mg/kg bw/d)	(trigger 10)
medium herbivorous mammal
acetamiprid	0.28	87	0.046	1.3*	1.5	213	146

* Worst case value, for interval 14 days (MAF for interval 30 days is not given in de guidance document).

Table E.8b Long-term risk for mammals

Substance	FIR / bw	RUD	Applica-tion rate (kg a.s./ha)	MAF	ftwa	Long-term ETE	NOEL (mg/kg bw/d)	TER
Substance	FIR / bw	RUD	Applica-tion rate (kg a.s./ha)		ftwa	(mg/kg bw/d)	NOEL (mg/kg bw/d)	(trigger 5)
medium herbivorous bird
acetamiprid	0.28	40	0.046	1.14	0.53	0.31	15	48

Taking the results in Table E.8 into account, it appears that all proposed uses meet the standards laid down in the RGB.

drinking water

The risk from exposure through drinking from surface water is calculated for a small mammal with body weight 10 g and a DWI (daily water intake) of 1.57 g/d. Surface water concentrations are calculated using TOXSWA (see paragraph 6.2.1). In the first instance, acute exposure is taken into account. The highest PIEC_wateris 0.300 mg/L. It follows that the risk of drinking water is (LD50 * bw) / (PIEC*DWI) = (213 * 0.010) / (0.000300 * 0.00157) = 4.5*10⁶. Since TER >> 10, the risk is acceptable.

7.3.2 Secondary poisoning

The risk as a result of secondary poisoning is assessed based on bioconcentration in fish and worms.

Since the log Kow of acetamiprid and metabolites < 3 (see 7.1.2), the potential for bioaccumulation is considered low and no further assessment is deemed necessary.

Conclusions mammals

The product complies with the RGB.

7.4 Effects on bees

The risk assessment for bees is based on the ratio between the highest single application rate and toxicity endpoint (LD₅₀ value). An overview of the risk at the proposed use with the highest exposure is given in Table E.9.

Table E.9 Risk for bees

Use	Substance	Application rate	LD₅₀	Rate/LD₅₀	Trigger value
		[g a.s./ha]	[µg/bee]
Production of flower bulbs, flower tubers and bulb flowers	acetamiprid	50	8.09	6.2	50

Since the ratio rate/LD₅₀ is below 50, the risk for bees is considered to be low. Hence, all proposed uses meet the standards for bees as laid down in the RGB.

Conclusions bees

The product complies with the RGB.

7.5 Effects on any other organisms (see annex IIIA 10.5-10.8)

7.5.1 Effects on non-target arthropods

The risk for non-target arthropods is assessed by calculating Hazard Quotients. For this, Lethal Rate values (LR₅₀) are needed. Based on LR₅₀-values from studies with the two standard species Aphidius rhopalosiphi and Typhlodromus pyri an in-field and an off-field Hazard Quotient (HQ) can be calculated according to the assessment method established in the SETAC/ESCORT 2 workshop and described in the HTB (v 1.0). Hazard Quotients should be below the trigger value of 2 to meet the standards. However, first tier laboratory tests obtained 100% mortality at relevant doses, therefore a second tier assessment, using extended laboratory studies, is performed. In the second tier HQ can be calculated for both lethal and sublethal effects. The HQ values should be < 1. For T.pyri an LR50 of 29.7 g a.s./ha is available; for A. rhopalosiphi an LR50 of 9.7 g a.s./ha is available from extended lab tests. At these concentrations, no effects on reproduction were found. ER₅₀ values are therefore > LR₅₀values. For greenhouse uses only in-field risk is considered.

The resulting Hazard Quotients are presented in Table E.10.

Table E.10 HQ-values for A. rhopalosiphi and T. pyri

	Application rate (g a.s./ha)	MAF¹	Drift factor/ Vegetation factor²	Safety factor²	LR₅₀ (g a.s./ha)	HQ
Production of flower bulbs, flower tubers and bulb flowers, field use
In-field
A. rhopalosiphi	46	2.3	-	-	9.7	10.9
T. pyri	46	2.3	-	-	29.7	3.56
Off-field
A. rhopalosiphi	46	2.3	0.1	5	9.7	5.5
T. pyri	46	2.3	0.01	5	29.7	0.18
Production of flower bulbs, flower tubers and bulb flowers, glasshouse use
In-field
A. rhopalosiphi	50	3.2	-		9.7	16.5
T. pyri	50	3.2	-		29.7	5.4

¹: Multiple Application Factor

²: off-field: drift factor = 10% for field uses; vegetation distribution factor = 10 (not used when whole plans were sprayed in the test); safety factor = 5 (for extended lab tests).

As the above table shows, in-field HQ values are above the trigger value of 1. Furthermore, the off-field HQ-value for A.rhopalosiphi is above the trigger value of 1. Based on the data presented above an in-field and off-field risk for non-target arthropods cannot be excluded. Higher tier studies are therefore required.

Refined risk assessment

Acetamiprid degrades quickly from all kinds of substrates. The DT50 is soil is 7.7 days, in water 24.8 days and from crop residue studies it appears that residues have disappeared within a week. The metabolites did not show any insecticidal activity. Considering the relatively long interval for the field use, the MAF could be set on 1 for uses with intervals of ≥20 days (in accordance with the monograph). Based on a MAF of 1, the off-field HQ for A.rhopalosiphi is still above the trigger value of 1 (2.4) based on the effects from initial residues.

In the addendum to the monograph several aged residue tests are evaluated. Both T. pyri and A. rhopalosiphi were tested at single applications of 13 and 100 g a.s./ha. For A. rhopalosiphi, 90% effects on mortality was found at 13 g a.s./ha, but this effect was < 50% at 7 days of ageing. At 100 g a.s./ha, effects were < 50% at 14 days ageing. This shows that a quick recovery is possible. Considering the mobility of A. rhopalosiphi and the short duration of effects, an acceptable risk is expected for all field applications both off-and in-field.

For T. pyri, no effect > 50% were found at the test rate of 13 g a.s./ha. At 100 g a.s./ha, no effect > 50% were found at 14 days ageing. Since no off-field risk was expected and recovery of the in-field could take place after 14 days, an acceptable risk is expected for all field applications.

Other arthropods: Coccinella septempunctata and Chrysoperla carnea

For C. septempunctata no effects > 50% were found at 13 g a.s./ha. No effects > 50% a.s./ha were found at 100 g a.s./ha, after 7 days ageing. For C. carnea no effect > 50% were found at day 0 in both the 13 g a.s./ha and 100 g a.s./ha treatment. Therefore an acceptable risk is expected for all field applications.

Greenhouse applications

Other ‘in-field’ criteria apply where natural enemies (‘beneficials’) in integrated pest management systems (such as greenhouse crops, fruit growing, tree nursery crops) are concerned. Effects on beneficials higher than or equal to 30% in the first tier and higher than or equal to 25% for higher tiers are in that case not acceptable, even if recovery occurs at short term.

Since an in-field risk is expected for all arthropods tested, the following warning sentence should be placed on the label (in Dutch):

“Dit middel is schadelijk voor niet-doelwit arthropoden. Vermijd onnodige blootstelling.”

Hence, the standards for non-target arthropods are met, if a warning sentence is placed on the label.

7.5.2 Earthworms

For the glasshouse use, management practice includes regular sterilisation of the soil, which prevents the formation of a natural soil organism community within glasshouses. Exposure to natural soils is not expected. Therefore no risk assessment is performed for soil organisms.

For the field use, the acute risk for earthworms is calculated as TER-value(trigger value 10). Since the logPow of the active substance < 2, no correction to the reference soil containing 4.7 % organic matter is necessary. Exposure is expressed as the initial PEC soil. PEC soil is calculated in section 6.1.1. Table E.11 presents endpoints, PECsoil and TER values.

Table E.11 Overview of soil concentrations and acute TERs for earthworms

Use

Substance

LC50_corr

[mg/kg]

PIECsoil

[mg/kg]

TER

Trigger value

Production of flower bulbs, flower tubers and bulb flowers, field use

Acetamiprid

0.050

180

Gazelle

3.66

0.050

73.2

In view of the results presented in Table E.11, a low acute risk for earthworms is expected at all proposed uses.

In the subchronic risk assessment for earthworms, a long-term TER-value is calculated. Examination of the PIEC takes place against the trigger of 0.2*NOEC. See Table E.12.

Table E.12 Overview of soil concentrations and chronic TERs for earthworms

Use

Substance

NOEC_corr

[mg/kg]

PIECsoil

[mg/kg]

TER

Trigger value

Production of flower bulbs, flower tubers and bulb flowers, field use

Gazelle

0.252

0.050

5.04

The chronic threshold value for earthworms resulting from exposure to acetamiprid is not exceeded. The proposed applications of the product therefore meet the standards as laid down in the RGB.

Metabolites

Metabolite IM-1-4 and IC-0 are relevant in soil. Given the lower expected concentration of IM-1-4 (see section 6.1) and the lower toxicity of both metabolites than the parent, the risk for these metabolites is covered in the risk assessment for acetamiprid.

Metabolites IM-1-5 and IM-1-2 occur only in calcareous soils (pH > 8). Although in the Netherlands some calcareous soils are present, the pH in agricultural soils is < 8 (See also C 167.3.13). Therefore these metabolites are not further assessed.

7.5.3 Effects on soil micro-organisms

For glasshouse uses, management practice includes regular sterilisation of the soil, which prevents the formation of a natural soil organism community within glasshouses. Exposure to natural soils is not expected. Therefore no risk assessment is performed for soil organisms.

For field uses, risk assessment is necessary. In the tested soils no effects are observed on nitrogen transformation and carbon respiration processes at relevant application rates of 0.2 kg a.s./ha with the formulated product Gazelle. Since the reduction percentage is below 25% after 28 days, the standards regarding soil micro-organisms are met.

7.5.4 Effects on activated sludge

An EC₅₀ value of >1000 mg/L is available.

Greenhouse use

The trigger is set to 0.1* EC₅₀ corresponding to >100,000 µg/L. The concentration in the influent of the sewage treatment plant (STP) has to be examined against this trigger using the model application USES. However, to date there is no module available to calculate influent concentrations for most application types (with the exception of mushroom use, public gardens and amenity uses).

Therefore, the proposed application cannot be examined against the standard for activated sludge as laid down in the RGB. For the time being this issue is not taken into consideration.

Field use

For the proposed field use no exposure of activated sludge is expected. Therefore, the proposed applications comply with the standards for activated sludge as laid down in the RGB.

7.5.5 Effects on non target-plants

The risk assessment for non-target plants is based on an off-crop situation with a drift percentage of 4.7%. The exposure from the field uses thus equals 0.047 * the application rate * MAF = 0.047 * 46 * 2.3 = 5 g a.s./ha. For the glasshouse uses, no exposure is expected to off-field areas.

For acetamiprid, only screening data is available. For all species tested, no effects were found (both in lab and field). The highest dose tested was 100 g a.s./L. Considering that no effects were found on any of the species at a dose far above the expected off-field dose and taking into account the fast dissipation of acetamiprid, an acceptable risk is expected for non-target plants.

Conclusions any other organisms

The product complies with the RGB for the aspects non-target arthropods, earthworms, soil micro-organisms, activated sludge and non-target plants.

7.6 Appropriate ecotoxicological endpoints relating to the product and approved uses

See List of Endpoints.

7.7 Data requirements

None.

7.8 Classification and labelling

Proposal for the classification of the active ingredient acetamiprid (symbols and R phrases)

Symbol:	-	Indication of danger: -
Risk phrases	R52/53	Harmful to aquatic organisms, may cause long-term adverse effects in the aquatic environment.

Proposal for the classification and labelling of the formulation concerning the environment

Based on the profile of the substance, the provided toxicology of the preparation and the http://www.interglot.com/toclipboard.php?b=1&d=2&t=eigenschap&s=karakterisering&w=characteristic characteristics of the co-formulants, the following labeling of the preparation is proposed:

Symbol:	-	Indication of danger:	-
R phrases	R-	-

S phrases	S-	-
Special provisions (DPD-phrases) :	-	-

The following restriction sentences were proposed by the applicant:

“Dit middel is schadelijk voor niet-doelwit arthropoden. Vermijd onnodige blootstelling.”

Based on the current assessment, the following has to be stated in the GAP/legal instructions for use:

In the legal instructions for use (WG) the following has to be stated:

“Dit middel is schadelijk voor niet-doelwit arthropoden. Vermijd onnodige blootstelling.”

7.9 Overall conclusions regarding ecotoxicology

It can be concluded that:

all proposed applications of the active substance acetamiprid meet the standards for birds as laid down in the RGB.
all proposed applications of the active substance acetamiprid meet the standards for aquatic organisms as laid down in the RGB.
the active substance acetamiprid meets the standards for bioconcentration as laid down in the RGB.
all proposed applications of the active substance acetamiprid meet the standards for mammals as laid down in the RGB.
all proposed applications of the active substance acetamiprid meet the standards for bees as laid down in the RGB.
all proposed applications of the active substance acetamiprid meet the standards for non-target arthropods as laid down in the RGB.
all proposed applications of the active substance acetamiprid meet the standards for earthworms as laid down in the RGB.
all proposed applications of the active substance acetamiprid meet the standards for soil micro-organisms as laid down in the RGB.
all proposed field applications of the active substance acetamiprid meet the standards for activated sludge as laid down in the RGB.
all proposed glasshouse applications of the active substance acetamiprid cannot be examined against the standards as laid down in the RGB; for the time being this issue is not taken into consideration.
all proposed applications of the active substance acetamiprid meet the standards for non-target plants as laid down in the RGB

8. Efficacy

This evaluation is partly based on the summary and evaluation of Gazelle prepared by Linge Agroconsultancy on behalf of the applicant (Report: Lds08certis12).

8.1 Efficacy evaluation

Dose justification

No effectiveness trials were carried out. Gazelle already has an authorisation in the Netherlands. Gazelle is authorised against a wide range of aphids in a large number of crops. All aphids which are claimed for label extension in flower bulbs and bulb flowers are already registered in other crops on the label. It may be assumed that for the authorisation the optimal dose rate has been proven and evaluated.

Effectiveness

No effectiveness trials were carried out. Gazelle already has an authorisation in the Netherlands. For label extension in flower bulbs and bulb flowers (protected and unprotected) no efficacy trials are needed. The reason is that Gazelle is authorised against a wide range of aphids in a large number of crops. All aphids which are claimed for label extension in flower bulbs and bulb flowers are already registered in other crops on the label. Effectiveness has already been proven, as well in indoor (glasshouse) grown crops as outdoor grown crops. The registered dose rate in protected cultivations is the same as the claimed dose rate in protected flower bulbs. For unprotected cultivations the registered dose rate is somewhat higher (250 g/ha) than the claimed dose rate (230 g/ha) in unprotected flower bulbs. Because this lower dose rate of 230 g/ha is within a 10% range, no change in efficacy is expected.

Conclusion

The product complies with the Uniform Principles because it does in accordance with article 2.1

control aphids in flower bulbs and bulb flowers.

8.2 Harmful effects

8.2.1 Phytotoxicity

18 phytotoxicity trials were conducted in the Netherlands during 2007 and 2008. The trials were carried out in three different flower bulb crops (forcery of lily, tulip and iris). For each crop 6 different cultivars were used. Dose rates tested for Gazelle were 50 g ai/ha (n) and 100 g ai/ha (2n). The standard product based on thiacloprid was tested in a dose rate of 120 g ai/ha (n) and 240 g ai/ha (2n).

Assessments were made on phytotoxicity, crop condition/stand, visible residue (spray deposit) and colour of the flowers. No phytotoxic effects nor visible residues were observed in the trials. Gazelle did not have a negative effect on crop condition/stand and colour of the flowers.

8.2.2 Yield

Yield was not determined. This is, however, not required.

8.2.3 Effects on succeeding crops or substitution crops

Gazelle already has an authorisation in the Netherlands. No adverse effects are known. Moreover, DT-50 and DT-90 values in soil under aerobic laboratory conditions are 1.4 and 4.7 days, respectively. When the proposed product is applied in accordance with good agricultural practises, it is not probable that Gazelle will have an effect on succeeding crops/substitution crops.

8.2.4 Effects on plants or plant products to be used for propagation

Gazelle already has an authorisation in the Netherlands. No adverse effects are known. In general, neonicotinoid insecticides – the chemical family of Gazelle – does not affect parts or parts used for propagation purposes. When the proposed product is applied in accordance with good agricultural practises, it is not probable that Gazelle will have an effect on parts or plants used for propagation purposes.

8.2.5 Effects on adjacent crops

Gazelle already has an authorisation in the Netherlands. No adverse effects are known. When the proposed product is applied in accordance with good agricultural practises, it is not probable that Gazelle will have an effect on adjacent crops.

Conclusion

The product complies with the Uniform Principles because it does not, in accordance with article 2.2., induce any unacceptable side effects on plants or plant products, when used and applied in accordance with the proposed label.

8.3 Resistance

Acetamiprid is classified by the Insecticide Resistance Action Committee (IRAC) due to the primary site of action in the main group 4 of the nicotinic acetylcholine receptor agonists/ antagonists. This class of materials functions by binding to the nicotinic acetylcholine receptor in the postsynaptic neurons of the insect central nervous system. This binding causes the ion pore in the receptor to open and allows an overloading of the postsynaptic cells with sodium ions. This leads to hyper excitation of the nervous system and eventual death of the insect.

The chemical sub-group for acetamiprid is the group 4A of the neocotinoids. More active ingredients of the chemical class are imidachloprid, thiacloprid, and thiamethoxam. Since their introduction, they have a broad spectrum of use in the agriculture and horticulture and the development of reduced susceptibility is known.

To reduce the risk of reduced susceptibility, it is recommended to alternate Gazelle with products with an other mode of action that are authorised for this purpose. This recommendation is included in the label text.

Conclusion

The product complies with the Uniform Principles, article 2.1.3 as the level of control on the long term is not influenced by the use of this product because of the possible build up of resistance.

8.4 For vertebrate control agents: impact on target vertebrates

Because no vertebrates are controlled, this point is not relevant.

8.5 Any other relevant data / information / Data requirements

None.

9. Conclusion

The product complies with the Uniform Principles.

The evaluation is in accordance with the Uniform Principles laid down in appendix VI of Directive 91/414/EEC. The evaluation has been carried out on basis of a dossier that meets the criteria of appendix III of the Directive.

10. Classification and labelling

Proposal for the classification and labelling of the formulation

Based on the profile of the substance, the provided toxicology of the preparation, the characteristics of the co-formulants, the method of application and the risk assessments, the following labelling of the preparation is proposed:

Substances, present in the formulation, which should be mentioned on the label by their chemical name (other very toxic, toxic, corrosive or harmful substances):
-
Symbol:	Xn	Indication of danger:	Harmful
R phrases	R22	Harmful if swallowed.

S phrases	S21 S22 S36/37 S46	When using do not smoke Do not breathe dust. Wear suitable protective clothing and gloves. If swallowed, seek medical advice immediately and show this container or label.

Special provisions: DPD-phrases	-	-
Plant protection products phrase: DPD-phrase	DPD01	To avoid risk for man and the environment, comply with the instructions for use
Child-resistant fastening obligatory?			n/a
Tactile warning of danger obligatory?			n/a

In the legal instructions for use (WG) the following has to be stated:

“Dit middel is schadelijk voor niet-doelwit arthropoden. Vermijd onnodige blootstelling.”

[1] INS: international and national quality standards for substances in the Netherlands.

[2] RIVM: National institute of public health and the environment.

[3] 601782001/2007: P.L.A. van Vlaardingen and E.M.J. Verbruggen, Guidance for the derivation of environmental risk limits within the framework of 'International and national environmental quality standards for substances in the Netherlands' (INS). Revision 2007’.

gevaarsymbool:	aanduiding:
Xn	Schadelijk

Annex point	Author	Year	Title Source (where different from company) Company, Report No. GLP or GEP status (where relevant) Published or Unpublished	Data protection claimed Y/N	Owner	Application number*	Date of submission*	Studie gebruikt y/n
KIIIA 2.7.5/01	Woolley, A.J.	2007	Acetamiprid 20SG: Determination of Long-Term Storage Stability and Physico-Chemical Characteristics. Report no.: RD-01284 GLP, Unpublished	Y	Certis Europe BV	20080981 UG	18-03-2010	y
KIIIA 6.1.3/01	Van Harinxma, W.J.	2007	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2007. Agro Research International B.V. Report no.: ARI-07-S-028-01 (I07.135.ARI-1). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y
KIIIA 6.1.3/02	Van Harinxma, W.J.	2007	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2007. Agro Research International B.V. Report no.: ARI-07-S-028-02 (I07.135.ARI-2). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y
KIIIA 6.1.3/03	Van Harinxma, W.J.	2007	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2007. Agro Research International B.V. Report no.: ARI-07-S-028-03 (I07.135.ARI-3). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y
KIIIA 6.1.3/04	Van Harinxma, W.J.	2008	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2008. Agro Research International B.V. Report no.: ARI-07-S-028-04 (I07.135.ARI-4). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y
KIIIA 6.1.3/05	Van Harinxma, W.J.	2008	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2008. Agro Research International B.V. Report no.: ARI-07-S-028-05 (I07.135.ARI-5). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y
KIIIA 6.1.3/06	Van Harinxma, W.J.	2008	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2008. Agro Research International B.V. Report no.: ARI-07-S-028-06 (I07.135.ARI-6). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y
KIIIA 6.1.3/07	Van Harinxma, W.J.	2007	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2007. Agro Research International B.V. Report no.: ARI-07-S-028-07 (I07.135.ARI-7). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y
KIIIA 6.1.3/08	Van Harinxma, W.J.	2007	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2007. Agro Research International B.V. Report no.: ARI-07-S-028-08 (I07.135.ARI-8). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y
KIIIA 6.1.3/09	Van Harinxma, W.J.	2007	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2007. Agro Research International B.V. Report no.: ARI-07-S-028-09 (I07.135.ARI-9). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y
KIIIA 6.1.3/10	Van Harinxma, W.J.	2008	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2008. Agro Research International B.V. Report no.: ARI-07-S-028-10 (I07.135.ARI-10). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y
KIIIA 6.1.3/11	Van Harinxma, W.J.	2008	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2008. Agro Research International B.V. Report no.: ARI-07-S-028-011 (I07.135.ARI-11). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y
KIIIA 6.1.3/12	Van Harinxma, W.J.	2008	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2008. Agro Research International B.V. Report no.: ARI-07-S-028-12 (I07.135.ARI-12). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y
KIIIA 6.1.3/13	Van Harinxma, W.J.	2007	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2007. Agro Research International B.V. Report no.: ARI-07-S-028-13 (I07.135.ARI-13). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y
KIIIA 6.1.3/14	Van Harinxma, W.J.	2007	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2007. Agro Research International B.V. Report no.: ARI-07-S-028-14 (I07.135.ARI-14). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y
KIIIA 6.1.3/15	Van Harinxma, W.J.	2007	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2007. Agro Research International B.V. Report no.: ARI-07-S-028-15 (I07.135.ARI-15). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y
KIIIA 6.1.3/16	Van Harinxma, W.J.	2008	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2008. Agro Research International B.V. Report no.: ARI-07-S-028-16 (I07.135.ARI-16). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y
KIIIA 6.1.3/17	Van Harinxma, W.J.	2008	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2008. Agro Research International B.V. Report no.: ARI-07-S-028-17 (I07.135.ARI-17). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y
KIIIA 6.1.3/18	Van Harinxma, W.J.	2008	Evaluation Of Paf 05 001 In Flower Bulbs (Forcery) For Crop Safety The Netherlands – 2008. Agro Research International B.V. Report no.: ARI-07-S-028-18 (I07.135.ARI-18). GEP. Unpublished.	Y	Certis Europe BV	20080981 UG	18-11-2008	y

werkzame stof:	gehalte:
acetamiprid	20 %