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HET COLLEGE VOOR DE TOELATING VAN GEWASBESCHERMINGSMIDDELEN EN BIOCIDEN

BIJLAGE II bij het besluit d.d. 5 november 2010 tot uitbreiding van de toelating van het middel Infinito, toelatingnummer 12927 N

Contents Page

1. Identity of the plant protection product 2

2. Physical and chemical properties 4

3. Methods of analysis 11

4. Mammalian toxicology 16

5. Residues 32

6. Environmental fate and behaviour 39

7. Ecotoxicology 86

8. Efficacy 109

9. Conclusion 109

10. Classification and labelling 109

1. Identity of the plant protection product

1.1 Applicant

Bayer CropScience

Energieweg 1

3641 RT Mijdrecht

The Netherlands

1.2 Identity of the active substance

Fluopicolide

Common name	fluopicolide
Name in Dutch	fluopicolide
Chemical name	2,6-dichloro-N-[3-chloro-5-(trifluoromethyl)-2-pyridylmethyl]benzamide [IUPAC]
CAS no	239110-15-7
EC no	Not allocated

The active substance was included on June 1^st,, 2010 in Annex I of Directive 91/414/EEC.

Propamocarb

Common name	propamocarb
Name in Dutch	propamocarb
Chemical name	propyl 3-(dimethylamino) propylcarbamate (propamocarb) propyl 3-(dimethylamino)propylcarbamate hydrochloride (propamocarb hydrochloride)
CAS no	24579-73-5 (propamocarb) 256606-41-1 (propamocarb hydrochloride)
EC no	247-125-9 (propamocarb hydrochloride) propamocarb: not allocated

The active substance was included on October 1^st, 2007 in Annex I of Directive 91/414/EEC.

The active substance is formulated as its variant propamocarb hydrochloride, which is included in the evaluation of the active substance propamocarb in Annex I of Directive 91/414/EEC.

1.3 Identity of the plant protection product

Name

Infinito

Formulation type

Content active substance

Fluopicolide: 62.5 g/L pure active substance

Propamocarb hydrochloride: 625 g/L pure propamocarb hydrochloride, which is equal to 525.2 g/L pure propamocarb

The formulation is part of the assessment of the active substance fluopicolide for inclusion in Annex I of Directive 91/414/EEC.

The formulation is not part of the assessment of the active substance propamocarb for inclusion in Annex I of Directive 91/414/EEC.

1.4 Function

Fungicide.

1.5 Uses applied for

See GAP (Appendix 1).

1.6 Background to the application

Extension of the authorization for non professional uses.

1.7 Packaging details

1.7.1 Packaging description

Material:	HDPE
Capacity:	100 ml, 1, 5 or 10L
Type of closure and size of opening:	100 ml: child resistant cap with foam disk, 29 mm opening 1, 5 or 10L: Screw cap 36, 50 or 63mm with HF seal or internal wad or linerless
Other information	ADR and 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 substances

Identity (fluopicolide)

Fluopicolide is a new active substance, included in Annex I of Directive 91/414/EEC. The final List of Endpoints presented below is taken from the EFSA Scientific report on fluopicolide (2009) 299; 1-158 (d.d. 4 June 2009), also taking into account the final draft review report on fluopicolide (SANCO/10164/2009 – rev 4, to be published 27 November 2010). Where relevant, some additional remarks/information are given in italics.

Active substance (ISO Common Name)	Fluopicolide
Chemical name (IUPAC)	2,6-dichloro-N-{[3-chloro-5-(trifluoromethyl)-2-pyridinyl]methyl}benzamide
Chemical name (CA)	benzamide, 2,6-dichloro-N-[[3-chloro-5-(trifluoromethyl) -2-pyridinyl]methyl]
CIPAC No	787
CAS No	239110-15-7
EEC No (EINECS or ELINCS)	not yet allocated
FAO Specification (including year of publication)	None
Minimum purity of the active substance as manufactured (g/kg)	970 g/kg
Identity of relevant impurities (of toxicological, environmental and/or other significance) in the active substance as manufactured (g/kg)	Toluene: max 0.3%
Molecular formula	C₁₄H₈Cl₃F₃N₂O
Molecular mass	383.59
Structural formula

Physical-chemical properties

Melting point (state purity)	150°C (99.3%)
Boiling point (state purity)	Not measurable, decomposes above 320°C
Temperature of decomposition (state purity)	>320°C (99.3%)
Appearance (state purity)	Beige solid (pure 99.3 % and technical 96.1 %)
Relative density (state purity)	1.65 g/cm³ at 4°C (Relative) (99.3%)
Surface tension	71.3 mN/m at 20C (concentration = 2.52 mg/l) (96.1%)
Vapour pressure (state temperature, state purity)	3.03 x 10^-7 Pa at 20°C (99.6%)
Henry’s law constant (in Pa·m³·mol^-1)	4.15 x 10^-5 Pa m³ mol^-1
Solubility in water (state temperature, state purity and pH)	0.0028g/l at pH7 and 20C (solubility is independent of pH) (99.3%)
Solubility in organic solvents (state temperature, state purity)	n-hexane 0.2g/l at 20°C (99.3%) dichloromethane 126g/l at 20°C (99.3%) ethanol 19.2g/l at 20°C (99.3%) toluene 20.5g/l at 20°C(99.3%) acetone 74.7g/l at 20°C(99.3%) ethyl acetate 37.7g/l at 20°C(99.3%) dimethylsulfoxide 183g/l at 20°C(99.3%)
Partition co-efficient (log P_ow) (state temperature, pH and purity)	Log Pow = 2.9 at 20C (pH7 ) (Log Pow is independent of pH) (99.3%)
Hydrolytic stability (DT₅₀) (state pH and temperature)	Hydrolytically stable at pH 4, 7 and 9 after 30 days at 25°C
Dissociation constant (state purity)	No dissociation (96.1%)
UV/VIS absorption (max.) incl ε at state purity, pH)	Purity (99.3%) neutral, methanol solution: lmax (nm); ε (L.mol-1.cm-1) 203; 44519 271; 3601 No absorbance above 290nm. .
Photostability (DT₅₀) (aqueous, sunlight, state pH)	64 days at pH 7 and at 25°C
Quantum yield of direct photo- transformation in water at λ > 290 nm	z · 3.50x10 ^–2 mol · Einstein ^-1
Photochemical oxidative degradation in air	Atkinson calculation using AOPWIN v.1.90. Rate constant 4.757 x 10-12 cm3/molecule/sec. Atmospheric half life 3.373 days assuming 24 hour OH radical concentration of 0.5 x 106 radicals/cm3.
Flammability (state purity)	Not highly flammable (96.1%)
Auto-flammability	No self-ignition up to 401 ^oC
Explosive properties (state purity)	Non-explosive (96.1%)
Oxidising properties (state purity)	Non- oxidising (96.1)

Identity: propamocarb

Data on the identity and the physical and chemical properties is taken from the List of Endpoints (identity: EFSA Review Report, April 2007; physical and chemical properties: EFSA Scientific Report (2006) 78, 1-80 (d.d. 12 May 2006)). Changes and/or additions are taken up in italics.

Active substance (ISO Common Name)	propamocarb (unless otherwise stated, the following data relate to the variant propamocarb hydrochloride) The physical/chemical and residue evaluation related to the variant Propamocarb HCl. Parent Propamocarb was considered to be the residue definition from a residue viewpoint.
Chemical name (IUPAC)	Propyl 3-(dimethylamino)propylcarbamate (propamocarb) Propyl 3-(dimethylamino) propylcarbamate hydrochloride
Chemical name (CA)	Propyl [3-(dimethylamino)propyl]carbamate (propamocarb) carbamic acid, [3-dimethylaminopropyl]-, propyl ester, monochloride
CIPAC No	399 (Propamocarb) 399.601 (Propamocarb HCl)
CAS No	24579-73-5 (Propamocarb) 25606-41-1 (Propamocarb HCl)
EEC No (EINECS or ELINCS)	247-125-9 (Propamocarb HCl)
FAO Specification (including year of publication)	No FAO specification
Minimum purity of the active substance as manufactured (g/kg)	TC: 92% w/w, 920g/kg (Bayer CropScience) TK: 69% w/w, 749 g/L (Bayer CropScience) 920 g/kg (as propamocarb)
Identity of relevant impurities (of toxicological, environmental and/or other significance) in the active substance as manufactured (g/kg)	None identified
Molecular formula	C₉H₂₁ClN₂O₂
Molecular mass	224.7
Structural formula

Physical-chemical properties

Data is of the propamocarb hydrochloride variant unless otherwise specified.

Melting point (state purity)	64.2ºC(100.3% purity)
Boiling point (state purity)	Product decomposed at 150ºC (99.1% purity)
Temperature of decomposition	150ºC (99.1% purity)
Appearance (state purity)	White/cream soft solid (97.2% purity)
Relative density (state purity)	1.16 at 20.5 ºC (97.2% purity)
Surface tension	71.98mN/m at 20ºC (97.2% purity) Concentration of test substance = 1g/L
Vapour pressure (in Pa, state temperature)	Two values have been submitted 8.1 x 10^-5Pa at 25ºC [97.7% purity] 1.66 x 10^-3Pa at 25ºC [99.1% purity] Test substance is slightly volatile
Henry’s law constant (in Pa·m³·mol^-1)	K = 8.5 x 10 ^–9 Pa m³ mol^-1.
Solubility in water (in g/l or mg/l, state temperature)	Between 89.2 and 93.5%w/w at pH 4 Between 89.1 and 93.8%w/w at pH 7 Between 89.6 and 94.6%w/w at pH 10 (20 ºC) Purity of test substance 99.1%
Solubility in organic solvents (in g/l, at 20 °C)	Solvent	g/l
	Hexane Toluene Methanol Dichloromethane Ethyl acetate Acetone Xylene Heptane Purity of test substance 100.0%	<0.01 0.04 >656 >626 4.8 560 1.6 x 10^-2 <1 x 10^-4
Partition co-efficient (log P_ow) (state pH and temperature)	Two values have been submitted Log P_OW= -2.9, -1.2 & 0.67 at pH 2, 7 & 9, respectively Log P_OW= -0.98, -1.4 & 0.32 at pH 2, 7 & 9, respectively
Hydrolytic stability (DT₅₀) (state pH and temperature)	<10% hydrolysis at pH 4, 7 & 9 at 50ºC over a five day period
Dissociation constant	pK_{a =}9.6 at 20ºC
UV/VIS absorption (max.) (if absorption >290 nm state ε at wavelength)	Absorption observed at λ 203 and 217nm at PH 7, in 0.1M HCl and in 0.1M NaOH. No absorbance >290nm.
Photostability (DT₅₀) (aqueous, sunlight, state pH)	No degradation of a.s. in aqueous solution when irradiated for 92hr. at 20ºC with a wavelength of λ >290nm.
Quantum yield of direct photo- transformation in water at λ > 290 nm	N.A. No photodegradation.
Photochemical oxidative degradation in air	DT₅₀= 4 hours (OH radical rate constant > 9.54x10^-11 cm³molecule^-1sec^-1)
Flammability	not flammable (TK)
Auto-flammability	312 ^oC (99.1%)
Oxidative properties	Not oxidising (theoretical assessment)
Explosive properties	Not explosive (99.1%)

2.2 Plant protection product: Infinito

Data about plant protection product are taken from studies submitted by the applicant.

The range of the application concentration of the plant protection product is 0.15 - 0.8 %

Section (Annex point)	Study	Guidelines and GLP	Findings	Evaluation and conclusion
B.2.2.1 (IIIA 2.1)	Appearance: physical state	GLP: no Visual	Liquid	Acceptable
B.2.2.2 (IIIA 2.1)	Appearance: colour	GLP: no Visual	Beige, opaque	Acceptable
B.2.2.3 (IIIA 2.1)	Appearance: odour	GLP: no Organoleptic	No odour	Acceptable
B.2.2.4 (IIIA 2.2)	Explosive properties	GLP: yes EC A14	Not explosive	Acceptable
B.2.2.5 (IIIA 2.2)	Oxidising properties	Theoretical assessment	Not oxidising, based on the properties of the product’s individual components	Acceptable
B.2.2.6 (IIIA 2.3)	Flammability		Not applicable
B.2.2.7 (IIIA 2.3)	Auto-flammability	GLP: yes EC A15	420 ^oC	Acceptable
B.2.2.8 (IIIA 2.3)	Flash point	Theoretical assessment	The product is water based and contains no flammable ingredients.	Acceptable
B.2.2.9 (IIIA 2.4)	Acidity / alkalinity		Not applicable
B.2.2.10 (IIIA 2.4)	pH	GLP: yes CIPAC MT75	1% dispersion: 7.0 (23 ^oC) Undiluted product: not determined	Acceptable. It is unlikely the undiluted product will have a pH of 4 or lower and therefore a study with the undiluted product is not required.
B.2.2.11 (IIIA 2.5)	Surface tension	GLP: yes EC A5	31 mN/m (1% dispersion)	Acceptable, because other triggers for labelling with Xn/R65 are not met.
B.2.2.12 (IIIA 2.5)	Viscosity	GLP: yes OECD 114 equivalent	At 20 ^oC: 20 s^-1: 221 mPa.s 100 s^-1 : 100 mPa.s	Acceptable, because other triggers for labelling with Xn/R65 are not met.
B.2.2.13 (IIIA 2.6)	Relative density	GLP: yes CIPAC MT3.3.1 / EC A3	Density: 1.130 g/ml (20 ^oC)	Acceptable
B.2.2.14 (IIIA 2.6)	Bulk (tap) density		Not applicable
B.2.2.15 (IIIA 2.7)	Storage stability	GLP: no CIPAC MT46.3	Stable for 2 weeks at 54 ^oC in HDPE. The following properties were determined before and after storage: content a.i., pH, wet sieve, pourability, suspensibility, spontaneity of dispersion, foam persistence, appearance, packaging stability.	Acceptable
B.2.2.15 (IIIA 2.7)	Storage stability	GLP: no CIPAC MT39.3	Stable for 7 days at 0 ^oC Suspensibility, spontaneity of dispersion and wet sieve tests were performed before and after storage.	Acceptable Content of toluene, the relevant impurity described in the List of Endpoints was not determined. This is considered acceptable, since toluene cannot be formed during manufacture or storage of the formulation.
B.2.2.16 (IIIA 2.7)	Shelf life	GLP: no CIPAC MT 75.2, 59.3, 148, 184, 160, 47.2 Analytical method: C-1094-01-03 P-1093-01-03	Stable for 2 years at ambient temperatures in HDPE packaging. The following properties were determined before and after storage: content a.i., pH, wet sieve, pourability, suspensibility, spontaneity of dispersion, foam persistence, appearance, packaging stability.	Acceptable
B.2.2.17 (IIIA 2.8)	Wettability		Not applicable
B.2.2.18 (IIIA 2.8)	Persistent foaming	GLP: no CIPAC MT47.2	0 ml after one minute (3.6 g/L and 9 g/L in CIPAC D water)	Acceptable
B.2.2.19 (IIIA 2.8)	Suspensibility	GLP: no CIPAC MT 184	Fluopicolide: 3.6 g/L (~0.36%): 98 - 100% 9 g/L (~0.9%): 99 - 100% Propamocarb: 3.6 g/L (~0.36%): 99% 9 g/L (~0.9%): 100%	Acceptable Based on the results it is considered acceptable that tests were not performed at the minimal application concentration of 0.15 % .
B.2.2.20 (IIIA 2.8)	Spontaneity of dispersion	GLP: no CIPAC MT160	100% for both active substances	Acceptable
B.2.2.21 (IIIA 2.8)	Dilution stability		Not applicable
B.2.2.22 (IIIA 2.8)	Dry sieve test		Not applicable
B.2.2.23 (IIIA 2.8)	Wet sieve test	GLP: no CIPAC MT59.3	< 0.1% retained on a 40 μm sieve. .	Acceptable A more fine sieve is used than the 75 μm sieve, which is considered acceptable
B.2.2.24 (IIIA 2.8)	Particle size distribution		Not applicable
B.2.2.25 (IIIA 2.8)	Content of dust/fines		Not applicable
B.2.2.26 (IIIA 2.8)	Attrition and friability		Not applicable
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		Not applicable
B.2.2.30 (IIIA 2.8)	Pourability (rinsibility)	GLP: no CIPAC MT148	2.7% residue	Acceptable
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		Not applicable
2.9.2	Chemical compatibility with other products		Not applicable

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

3.1. Analytical methods in technical material and plant protection product

Fluopicolide

Technical as (principle of method)

Fluopicolide in technical material was determined by HPLC-UV

Impurities in technical as (principle of method)

Organic impurities in technical material were determined by HPLC-UV

Water content was determined by Karl Fischer titration

Preparation (principle of method)

HPLC-UV, Method C-1094-01-03

Relevant impurity toluene: GC-FID

Propamocarb

Technical as (principle of method)

Test substance dissolved in methanol/water (80:20, v/v) and analysed using HPLC with UV detection.

Impurities in technical as (principle of method)

The following methods were used for analysis of the various impurities.

1. Test substance dissolved in dichloromethane, analysed using GC with FID detection.

2. Test substance dissolved in DMSO, equilibrated at 75°C prior to headspace injection and analysis using GC/FID.

3. Test material was dissolved in water, to which aqueous sodium hydroxide was added. Following extraction with dichloromethane, the aqueous solution was derivatized using benzoyl chloride and the resultant derivative extracted into dichloromethane and analysed using GC/FID.

4. Test material diluted in methanol/water was analysed using HPLC, with UV detection.

5. Test material was dissolved in water, diluted to 50ml with 1,4-dioxane and filtered. The sample was then analysed using GC/FID.

Preparation (principle of method)

Method P-1093-01-03

A CIPAC method for propamocarb is also available

Relevant impurity toluene: GC-FID

Conclusion

The analytical methods for propamocarb, fluopiclide and impurities in the technical material and the analytical method for the determination of propamocarb and fluopiclide in the preparation have been assessed in the DAR and are considered to be acceptable. The analytical method for the determination of the relevant impurity toluene in the formulation has been assessed and is considered to be acceptable.

3.2 Residue analytical methods

Fluopicolide

Food/feed of plant origin (principle of method and LOQ for methods for monitoring purposes)	Fluopicolide was determined by a modified version of the German multi residues method S19, with an LOQ of 0.1 mg/kg, 0.02 mg/kg and 0.02 mg/kg for (grape, wheat grain and potato respectively).
Food/feed of animal origin (principle of method and LOQ for methods for monitoring purposes)	Fluopicolide and its metabolites M-01 and M-02 in animal product were determined by HPLC/MS/MS, with an LOQ of 0.01 – 0.05 mg/kg. However, a method is not required as currently no MRLs are set for animal products.
Soil (principle of method and LOQ)	Fluopicolide and its metabolites M-01, M-03 and M-02 in soil were determined by HPLC/MS/MS, with an LOQ of 0.005 mg/kg
Water (principle of method and LOQ)	Fluopicolide and its metabolites M-01 and M-02 in water (tap and surface) were determined by HPLC/MS/MS, with an LOQ of 0.1 mg/l.
Air (principle of method and LOQ)	Fluopicolide was determined by GC/ECD and GC/MS with an LOQ of 3 mg/m³
Body fluids and tissues (principle of method and LOQ)	Not required as fluopicolide is not classified as toxic

Propamocarb

Food/feed of plant origin (principle of method and LOQ for methods for monitoring purposes)	Propamocarb residues were extracted with acetic acid (1% aqueous solution), eluted from C18 SPE with acetonitrile/water/acetic acid (20:80:1, v/v). Residues were determined by HPLC with MS/MS detection. Detection was at m/z = 189 (parent ion) –>102 + 144 (daughter ion). LOQ = 0.01 mg/kg. The method was independently validated for tomatoes and lettuce. The method is acceptable for analysis of residues of propamocarb and its salts in food/feed with high water content.
Food/feed of animal origin (principle of method and LOQ for methods for monitoring purposes)	An analytical method is not required due to fact that no MRL is proposed.
Soil (principle of method and LOQ)	1N Hydrochloric acid was added to soil and the samples were shaken on a horizontal flatbed shaker for approx. 60min., then centrifuged and the supernatant removed. The extracts were collected and brought to pH 6-7 with an ammonia solution (~25%). The extract was cleaned up on a C18 column and analysed using HPLC/MS/MS. Atmospheric pressure chemical ionisation (APCI) mode was used. The parent ion m/z 189 and two fragment ions m/z 102.1 and 144 were used for quantisation LOQ = 0.02mg/kg Soil samples were shaken in methanol/saturated NaCl (5:1, v/v) and the methanol fraction was evaporated. The aqueous fraction was adjusted to pH 3-4 using a 0.1N HCl solution. This was then washed with dichloromethane and the pH of the aqueous phase was adjusted to >11.5. Combined dichloromethane fractions were evaporated to dryness, reconstituted in methanol/water (80:20, v/v) and analysed using HPLC/MS/MS in the positive ion mode. The ions monitored were m/z 189.3 (parent ion) and m/z 102.3 (fragment ion). LOQ = 0.02mg/kg The method is acceptable for analysis of residues of propamocarb and its salts in soil
Water (principle of method and LOQ)	Alkaline treated water was extracted with dichloromethane. Dichloromethane was evaporated off and the extract reconstituted in a suitable solvent prior to analysis using HPLC/MS/MS in the positive ion mode. The ions monitored were m/z 189 (parent ion) and m/z 102 (fragment ion). The samples tested represented both drinking and surface water LOQ = 0.05µg/L The method is acceptable for analysis of residues of propamocarb and its salts in drinking and surface water
Air (principle of method and LOQ)	Two methods were considered suitable for analysis of residues of propamocarb in air. 1. Samples of air were drawn through silica gel adsorption tubes at a flow rate of ~0.3L/min. for a period of 6 hr. (total air sampling volume = 0.1m³). The silica gel was extracted three times with a mixture of acetonitrile/water/acetic acid/ammonia (200:800:10:2, v/v/v/v). The total combined extract was analysed using LC/MS/MS with atmospheric pressure chemical ionisation (APCI) source. Quantification was based on MS of the daughter ion peak 144m/z, resulting from the protonated molecular propamocarb ion observed at 189m/z. For further confirmation a second transition resulting in a daughter ion at 102m/z was included in the method. LOQ = 9µg/m³. 2. Tenax TA was spiked with a methanol solution of propamocarb. The efficiency of the extraction procedure with methanol/water (80:20) was assessed by recovery after 7.5hr. with an air flow of 3L/min. The degree of trapping was assessed by 2hr. and 7.5hr. recovery tests of samples, with an air flow of 3L/min at 35ºC and >80% relative humidity. The stability of propamocarb adsorbed on Tenax TA was demonstrated for a period of 14 days at ambient temperature and at -20ºC. Residues were determined by GC-MS-MS. LOQ = 0.4µg/m³
Body fluids and tissues (principle of method and LOQ)	Not required, non toxic compound

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 (potato).

Definition of the residue and proposed MRL’s for fluopicolide
Matrix	Proposed definition of the residue for monitoring	EU MRL
Food/feed of plant origin	Fluopicolide	0.02 mg/kg (potatoes)
Food/feed of animal origin	No definition of the residue is proposed. No relevant residues are expected to occur in food/feed of animal origin.
		Required LOQ
Soil	Fluopicolide	0.05 mg/kg
Drinking water	Fluopicolide	0.1 µg/L (Dutch drinking water guideline)
Surface water	Fluopicolide	29 µg/L (EbC50 for algae)
Air	Fluopicolide	0.15 mg/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.

Definition of the residue and MRL’s for propamocarb
Matrix	Definition of the residue for monitoring	EU-MRL
Food/feed of plant origin	Propamocarb	0.5 mg/kg
Food/feed of animal origin	No definition of the residue is proposed. No relevant residues are expected to occur in food/feed of animal origin.
		Required LOQ
Soil	Propamocarb	0.05 mg/kg (default)
Drinking water	Propamocarb	0.1 µg/L (drinking water guideline)
Surface water	Propamocarb	0.1 µg/L (HTB 1.0)
Air	Propamocarb	0.087 mg/m³ (derived from the AOEL (AOEL_systemic = 0.29 mg/kg bw/day) 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.

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

The residue analytical methods for water, soil and air, evaluated in the DAR, are acceptable and suitable for monitoring of residues of propamocarb 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 fluopicolide (symbols and R phrases)
(EU classification) concerning physical chemical properties

Symbol(s):

Indication(s) of danger: -

Risk phrase(s)

Proposal for the classification of propamocarb (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:	S21 is assigned to product which contain halogenated compounds which may form toxic fumes when incinerated or burned.
Other:	-

Supported shelf life of the formulation: 2 years

The proposed labelling above is equal to the previous decision regarding the labelling of the plant protection product Infinito (dated 1 June 2007).

4. Mammalian toxicology

List of Endpoints

Fluopicolide

Fluopicolide is a new active substance, included in Annex I of Directive 91/414/EEC. The final List of Endpoints presented below is taken from the EFSA Scientific Report on fluopicolide (2009) 299; 1-158 (d.d. 4 June 2009).The final review report on Fluopicolide is not yet available. Where relevant, some additional remarks/information are given in italics.

Impact on Human and Animal Health

Absorption, distribution, excretion and metabolism (toxicokinetics) (Annex IIA, point 5.1)
Rate and extent of oral absorption ‡	Moderately rapid absorption. Cmax in blood at 6 – 8 h. Approximately 62 % for the pyridyl radiolabel
Distribution ‡	Well distributed into organs and tissues. Highest concentrations in liver, kidneys, spleen and blood
Potential for accumulation ‡	No evidence of accumulation
Rate and extent of excretion ‡	Rapid and extensive (approximately 95 %) within 48 h mainly via faeces. Biliary fraction was approximately 52 % for the pyridyl radiolabel
Metabolism in animals ‡	Extensively metabolised. Biotransformations observed included aromatic ring hydroxylation, hydrolysis, dealkylation, acetylation, oxidative N-dealkylation and conjugation with glucuronic acid, sulphate and glutathione. Further metabolism of glutathione conjugates to cysteine conjugates.
Toxicologically relevant compounds ‡ (animals and plants)	Parent compound and M 01
Toxicologically relevant compounds ‡ (environment)	Parent compound

Acute toxicity (Annex IIA, point 5.2)
Rat LD₅₀ oral ‡	> 5000 mg/kg bw
Rat LD₅₀ dermal ‡	> 5000 mg/kg bw
Rat LC₅₀ inhalation ‡	> 5.16 mg/l (the mean achieved concentration, 4 h nose only)
Skin irritation ‡	Non-irritant
Eye irritation ‡	Non-irritant
Skin sensitisation ‡	Not sensitising (Buehler and Magnusson and Kligman methods)

Short term toxicity (Annex IIA, point 5.3)
Target / critical effect ‡	Liver, kidney, spleen and red blood cell parameters
Relevant oral NOAEL ‡	17.7 mg/kg bw/day; 28-day dietary study in rats 7.4 mg/kg bw/day; 90-day dietary study in rats 70 mg/kg bw/day; 90-day dog 300 mg/kg bw/day; 1-year dog
Relevant dermal NOAEL ‡	1000 mg/kg bw/day; 28-day dermal toxicity study in rats
Relevant inhalation NOAEL ‡	No data. Not required.

Genotoxicity ‡ (Annex IIA, point 5.4)
	No genotoxic potential ¹

¹ The genotoxic potential was investigated in 8 in vitro studies (5 Ames tests, 1 mammalian cell gene mutation test in Chinese hamster lung fibroblasts V79, 1 mammalian cytogenetic test in Chinese hamster lung fibroblasts V79, 1 mammalian cytogenetic test in human lymphocytes) and in 4 in vivo study (3 micronucleus tests in mouse bone marrow (2 oral, 1 i.p.) and 1 UDS test). Equivocal results were only obtained in one strain in 1 Ames test and in 1 oral micronucleus test.

Long term toxicity and carcinogenicity (Annex IIA, point 5.5)
Target/critical effect ‡	Liver: non-neoplastic lesions including centrilobular hepatocyte hypertrophy in the liver of rats and mice; and neoplastic lesions, hepatocellular adenomas in mice
Relevant NOAEL ‡	8.4. mg/kg bw/day in rats 7.9 mg/kg bw/day in mice
Carcinogenicity ‡	Hepatocellular adenomas in mice. Carcinogenic in mice by a mechanism considered to be not relevant in humans.

Reproductive toxicity (Annex IIA, point 5.6) Reproduction toxicity
Reproduction target / critical effect ‡	No specific evidence of reproductive toxicity. Birth weights were normal, however a reduction (ca. 8 – 14 %) in bodyweight gain in offspring in F₁ and F₂ generations at maternally toxic dose level of 103.4 mg/kg bw/day
Relevant parental NOAEL ‡	25.5 mg/kg bw/day
Relevant reproductive NOAEL ‡	103.4 mg/kg bw/day for F₀ males and 127.3 mg/kg bw/day for F₀ females for the period before pairing absence of reproductive toxicity at the highest test dose
Relevant offspring NOAEL ‡	25.5 mg/kg bw/day
Developmental toxicity
Developmental target / critical effect ‡	Reduction in mean foetal body weights and crown-rump lengths in foetuses in rats and rabbits at maternally toxic dose levels (60 mg/kg bw/day in rabbits and 700 mg/kg bw/day in rats). Maternal toxicity: reduced body weight in rats and rabbits; apparent exceptional toxicity was noted in rabbits including mortality, increased incidence of premature delivery and reduced food consumption
Relevant maternal NOAEL ‡	20 mg/kg bw/day in rabbits 60 mg/kg bw/day in rats
Relevant developmental NOAEL ‡	20 mg/kg bw/day in rabbits 60 mg/kg bw/day in rats

Neurotoxicity (Annex IIA, point 5.7)
Acute neurotoxicity ‡	Range-finding acute oral toxicity study: Peak effects in FOB tests were observed at approximately 6 hours. Acute neurotoxicity study: The NOAEL in the acute neurotoxicity study was 100 mg/kg bw based on reduction in body temperature and excessive grooming in females only at 2000 mg/kg bw in neurobehavioural screening.
Repeated neurotoxicity ‡	The NOAEL for neurotoxicity in the 90-day neurotoxicity study was 781 mg/kg bw/day based on the absence of abnormal responses in repeated neurobehavioural screening tests; The systemic NOAEL was 15 mg/kg bw/day based on liver and kidney findings.
Delayed neurotoxicity ‡	No data; not required

Other toxicological studies (Annex IIA, point 5.8)
Mechanism studies ‡	Mechanistic study to investigate liver toxicity in mice at a dose level of 3200 ppm for 28 days: - Increased Bromodeoxyuridine labelling index (ca.6.5 x at interim sacrifice on day 7 but not on day 28. - Evidence of increased Cytochrome P450 content and induction of the liver enzymes Benzoxyresofurin O-debenzylation, Ethoxyresofurin O-deethylation, pentoxyresofurin O-depentylation suggested indicating a phenobarbitone-type liver-enzyme induction and effects.
Studies performed on metabolites or impurities ‡	Extensive metabolism and toxicity studies including genotoxicity studies on metabolites: AE C653711 (M-01) AE C657188 (M-02) AE C657378 (M-04) AE 1344122 (M-05) AE 1344123 (M-10) AE 1388273 (M-14)
M01 or BAM
Toxicokinetic (M01)	Oral absorption: ca 82 % of the dose based on urine, cage wash and tissues six days after dosing. Distribution: highest concentration found in kidneys and liver. No potential for bioaccumulation. Excretion mainly via urine. Metabolism by hydrolysis of the amide group, hydroxylation and subsequent conjugation with glucuronic acid or sulphate, loss of chlorine atom following glutathione conjugation and further metabolism of the glutathione group to the mercapturic acid or S-methyl metabolites.
Acute toxicity (M01)	Rat LD₅₀ oral = 500 mg/kg bw (females); 2000 mg/kg bw (males) – acute toxic class method	Xn; R22
Short term toxicity (M01)	Target / critical effect: Decreased body weight gain, food intake and clinical signs Relevant oral NOAELs: 14 mg/kg bw/day (90-day rat) 22.5 mg/kg bw/day (90-day dog)
Genotoxicity (M01)	No genotoxic potential
Long term toxicity and carcinogenicity (M01)	Target / critical effect: Decreased body weight gain, liver toxicity (rat only) Relevant oral NOAELs: 5.7 mg/kg bw/day (2-year rat) 4.5 mg/kg bw/day (2-year dog) Carcinogenicity: No potential for carcinogenicity
Reproductive toxicity (M01)	Reproduction target / critical effect: No effect on reproduction. Parental and offspring’s reduced body weight. Organ weight changes in adults. Relevant parental, NOAEL: 7.5 mg/kg bw/day Relevant reproductive NOAEL: 13.5 mg/kg bw/day Relevant offspring NOAEL: 7.5 mg/kg bw/day
	Developmental target / critical effect: Maternal clinical signs; decreased body weight gain and food consumption. (rabbit) Relevant maternal NOAEL: 30 mg/kg bw/day Relevant developmental NOAEL: 30 mg/kg bw/day
ADI (M01)	0.05 mg/kg bw/day (2-year rat and dog studies; SF 100)
ARfD (M01)	0.3 mg/kg bw (developmental study in rabbit; SF 100)
M02
Toxicokinetic (M02)	Oral absorption: ca 87 % of the dose based on urine, cage wash and tissues six days after dosing. No potential for bioaccumulation. Excretion mainly unchanged via urine.
Acute toxicity (M02)	Rat LD₅₀ oral > 2000 mg/kg bw
Short term toxicity (M02)	Target / critical effect: None Relevant oral NOAELs: 1574 mg/kg bw/day (28-day rat)
Genotoxicity (M02)	No genotoxic potential
M04
Acute toxicity (M04)	Rat LD₅₀ oral > 2000 mg/kg bw
Short term toxicity (M04)	Target / critical effect: Liver and kidneys effects at 1775 mg/kg bw/day Relevant oral NOAELs: 159.2 mg/kg bw/day (28-day rat)
Genotoxicity (M04)	No genotoxic potential
M05
Acute toxicity (M05)	Rat LD₅₀ oral > 2000 mg/kg bw
Short term toxicity (M05)	Target / critical effect: Reduced body weight and kidney degeneration at 1495 mg/kg bw/day Relevant oral NOAELs: 152 mg/kg bw/day (28-day rat)
Genotoxicity (M05)	No genotoxic potential
M10
Acute toxicity (M10)	Rat LD₅₀ oral > 2000 mg/kg bw
Short term toxicity (M10)	Target / critical effect: Clinical signs and diarrhoea at 1748.2 mg/kg bw/day Relevant oral NOAELs: 163.8 mg/kg bw/day (28-day rat)
Genotoxicity (M10)	No genotoxic potential
M14
Genotoxicity (M14)	No genotoxic potential
	The metabolites were shown to be most likely non-genotoxic and were of lesser or comparable toxicity with the parent, fluopicolide. M-01, one of the principal metabolites was more acutely toxic than fluopicolide by the oral route tested (LD₅₀ of 500 mg/kg bw compared with 5000 mg/kg bw for the parent) but the NOAEL for chronic toxicity was comparable and or a similar order or magnitude to that of fluopicolide. Differences in findings and dose levels at LOAELs were noted. For the rotational crop metabolites not found in rat metabolism studies (M-04, M-05, M-08 and M-09) relevant data was provided for M-04 and M-05 as assessed above for groundwater metabolites, whilst M-08 and M-09 were shown to have substantial structural similarities with M-02 and predicted to share intermediate metabolic pathways and have similar toxicity profiles.

Medical data ‡ (Annex IIA, point 5.9)
	Limited; a new active ingredient

Summary (Annex IIA, point 5.10)	Value	Study	Safety factor
ADI ‡	0.08 mg/kg bw/day	78-week dietary study in mice, supported by the 2-year rat study	100
AOEL ‡	0.05 mg/kg bw/day	90 day dietary study in rats	161.3 (100 + 62 %*)
ARfD ‡	0.18 mg/kg bw/day	28-day dietary study in rats and the rabbit developmental study	100

* Correction for low oral absorption (62 %).

Dermal absorption ‡ (Annex IIIA, point 7.3) ²

Formulation (EXP11120A: SC containing 62.5 g fluopicolide/L and 625 g propamocarb hydrochloride/L)

Concentrate: 0.24 %

Spray dilutions: 2.75 %

Based on rat in vivo and comparative in vitro (human/rat skin)

²See4.2

Propamocarb-hydrochloride

Propamocarb is an existing active substance, included in Annex I of Directive 91/414/EEC. The final List of Endpoints presented below is taken from the EFSA Scientific Report on propamocarb (2006) 78; 1-80 (d.d. 12 May 2006), also taking into account the final review report on propamocarb (SANCO/10057/2006 – final, d.d. 25 April 2007). In the formulations included in the review report as well as in Infinito, propamocarb is present as propamocarb-hydrochloride. According to the review report the evaluated data also belong to the variant hydrochloride, unless otherwise specified. Where relevant, some additional remarks/information are given in italics.

Absorption, distribution, excretion and metabolism in mammals (Annex IIA, point 5.1)

Rate and extent of absorption ‡	Rapid (78 – 96%) within 72h
Distribution ‡	Mainly in organs associated with biotransformation (liver, lung, kidney). These were the only ones which had quantifiable amounts recorded (<0.17 mg equivalents/kg tissue). The highest transitory concentrations of radiolabel were detected in liver and kidneys between 0.75 and 3 hours post-dosing. Terminal half-life for all tissues was 11 – 26h
Potential for accumulation ‡	No evidence of accumulation
Rate and extent of excretion ‡	Rapid excretion - 91 to 94% within 72h for LD and HD respectively. Majority via urine (88 – 92% in 72h). Gender independent
Metabolism in animals ‡	Extensively metabolised with only between 1.1 and 11% excreted as unchanged propamocarb-anion in the low dose animals and up to 20% in high dose. Four major metabolites identified: 2-hydroxypropyl 3-(dimethylamino)propylcarbamate, propyl [3-(methylamino)propyl]carbamate, propyl-3-(dimethylamino)propylcarbamate-N-oxide and 3-(3-dimethylaminopropyl)-4-hydroxy-4-methyloxazolidin-2-one
Toxicologically significant compounds ‡ (animals, plants and environment)	Propamocarb hydrochloride, 2-hydroxypropyl 3-(dimethylamino)propylcarbamate, propyl [3-(methylamino)propyl]carbamate, propyl-3-(dimethylamino)propylcarbamate-N-oxide and 3-(3-dimethylaminopropyl)-4-hydroxy-4-methyloxazolidin-2-one

Acute toxicity (Annex IIA, point 5.2)

LD₅₀ oral	LD₅₀ > 2000 mg/kg bw
LD₅₀ dermal	LD₅₀> 2000 mg/kg bw
LC₅₀ inhalation	LC₅₀> 5.01 mg/L
Skin irritation	Non-irritant
Eye irritation	Non-irritant
Skin sensitization (result and test method used)	Sensitiser (9/20 animals sensitised) (Magnusson and Kligman) R43

Short term toxicity (Annex IIA, point 5.3)

Target / critical effect ‡¹	Vacuolar alterations of secretory epithelial cells in rat and dog. In the rat vacuolation occurred in the choroid plexus and lacrimal glands; in the dog vacuolation was evident in salivary glands, tracheal glands, lungs (bronchial glands), oesophagus, stomach (pyloric glands), duodenum (brunners glands), lacrimal glands and mandibular lymph nodes.
Lowest relevant oral NOAEL / NOEL ‡	< 39 mg/kg /day Propamocarb (lowest dose tested), in a 1-year dog feeding study. 45 mg/kg bw/day in 90 day dog study 100 mg/kg bw/day in 28 day rat study
Lowest relevant dermal NOAEL / NOEL ‡	300 mg/kg propamocarb, based on vacuolation of the choroid plexus in a 28-day rat study. Dermal irritation was observed at 71.7 mg/kg a.s. in a 21-day rat study.²
Lowest relevant inhalation NOAEL / NOEL ‡	No data, not required

¹In the DAR the following is stated: “The overall lowest relevant NOAEL was considered to be <39 mg/kg/day propamocarb hydrochloride, based on the vacuolar alterations observed in the 52-week dog study (Frieling, 2003). A proper NOAEL could not actually be determined exactly because in this 52-week dog study, vacuolation was observed at 1000 ppm, the lowest dose tested (equivalent to 39 and 42 mg/kg/day of active substance in males and females respectively). Therefore 39 mg/kg/day corresponds to the lowest LOEL rather than the NOEL. However, the vacuolation findings were all graded minimal to moderate and were not seen in all animals at this dose level. In addition, no effects were noted in the 90-day dog study at this dose level (Schoenmakers, 2001b). It is acceptable to assume that this dose can be considered as a threshold effect level and the NOEL for the above effects is only slightly lower than the threshold level. Moreover, the physiological meaning or adverse character of these lesions, i.e. their toxicological impact on the animal’s life (quality), appeared to be rather unobtrusive. A recovery period of 4 weeks (see 90-day rat study) did not abolish these findings but diminished the severity of vacuolation, suggesting, at least, partial reversibility. Finally, these lesions do not appear to affect all species: dog seems to be the most sensitive as well as rat to a lesser extent whereas vacuolation was not observed in mouse. In the dog the vacuolar changes appeared to be quite widespread, occurring within a range of secretory tissues and organs, whereas in the rat, the principle target organ appears to be the choroid plexus (and, in some cases, also the lacrimal glands). The toxicological significance to humans of these rather uncommon lesions remains therefore uncertain.”

²The List of Enpoints appears incorrect: In the DAR 2 short-term dermal toxicity studies in the rat are evaluated. In study 1, rats were dermally exposed for 5d/w during 3 weeks (occlusive exposure) to Previcur N. No systemic effects were observed (NOAEL 717 mg as/kg bw/d), dermal effects (scabbing and histopathologically dermatitis) were observed at 358 mg as/kg bw/d (NOAEL 71.7 mg as/kg bw/d). In study 2 (28 d study duration, exposure occlusive, 5d/w, tested formulation: Proplant), local and systemic effects were observed at 1200 mg as/kg bw/d (NOAEL 300 mg as/kg bw/d).

Genotoxicity ‡ (Annex IIA, point 5.4)

No genotoxic potential³

³ Negative in Ames tests, chromosome aberration studies in vitro and mammalian cell gene mutation tests in vitro. Also negative in the following in vivo studies: mouse micronucleus and dominant lethal essays.

Long term toxicity and carcinogenicity (Annex IIA, point 5.5)

Target/critical effect ‡	Vacuolar change, choroid plexus
Lowest relevant NOAEL / NOEL ‡	29 mg/kg bw/day (female rat; 52-week dietary study)
Carcinogenicity ‡	No evidence of carcinogenic potential

Reproductive toxicity (Annex IIA, point 5.6)

Parental/maternal critical effect ‡	Bodyweight, food consumption and vacuolar changes (F_o females)
Lowest relevant parental/maternal NOAEL / NOEL ‡	37 mg/kg bw/day as (rat, gavage)
Reproduction target / critical effect	Sperm concentration and count (F1 males)
Lowest relevant reproductive NOAEL / NOEL	37.5 mg/kg bw/day as (rat, gavage)
Developmental target / critical effect ‡	Increased number of small foetuses and ↓ weight of live foetuses
Lowest relevant developmental NOAEL / NOEL ‡	31 mg/kg bw/day (rat, dietary)

Neurotoxicity / Delayed neurotoxicity ‡ (Annex IIA, point 5.7)

Target / critical effects

Vacuolation of choroids plexus in ventricles of cerebrum and cerebellum

Lowest relevant NOAEL / NOEL

72(♂); 86(♀) (1500 ppm) from rat 90-day study

Acute neurotoxicity – no neurotoxicity at 1321 mg/kg bw (highest dose tested), NOAEL 134 mg/kg bw (reduced bodyweight)

Other toxicological studies ‡ (Annex IIA, point 5.8)

None available.

Medical data ‡ (Annex IIA, point 5.9)

No actual cases of human intoxication with propamocarb (hydrochloride) documented. The low animal toxicity of the active substance suggests accidental or occupational poisoning to be unlikely. No known cases of general ill health in production plant workers.

Summary (Annex IIA, point 5.10)	Value	Study	Safety factor
ADI ‡	0.29 mg propamocarb hydrochloride/kg bw/day	52-week dietary study in rats	100
AOEL_Systemic ‡⁴	0.29 mg propamocarb hydrochloride/kg bw/day	52-week dietary study in rats	100
ARfD ‡ (acute reference dose)	1 mg propamocarb hydrochloride/kg bw/day	28-day rat study (gavage)	100

⁴In the expert meeting, the experts noted that, based on the proposed pattern of use (e.g. greenhouses) a long term study was appropriate for the derivation of the AOEL, instead of the 90-day study in dogs, leading to an AOEL of 0.45 mg/kg bw/day. Therefore an AOEL of 0.29 mg propamocarb hydrochloride/kg bw/day was derived, based on the NOAEL of 29 mg/kg bw/day in the 52 week rat study was agreed with a safety factor of 100.

Dermal absorption (Annex IIIA, point 7.3)

In vivo dermal absorption, human

Provisional value of 10% for concentrate and dilution based on rat in vivo and rat/human in vitro (Previcur N).⁵

⁵ In the DAR, dermal absorption values from two in vivo rat studies were used (12% for the concentrated formulation and 10% for the spray strength dilution).

During the EPCO meeting, an addendum with the evaluation of a new in vitro rat/human skin study was produced by the rapporteur, which has not been peer reviewed. The rapporteur Member State proposes new, lower, dermal absorption values. EFSA proposes to remain with the provisional dermal absorption value of 10% and that the new study and evaluation by the rapporteur Member State is to be considered by MS at national level.

Local effects

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

Propamocarb-hydrochloride

Propamocarb-hydrochlide produces skin effects in a sensitisation study, but these effects are covered in the risk assessment/management by means of assignment of R- and S-phrases.

Propamocarb-hydrochloride produces skin irritation in a 21-day dermal toxicity study in rats with NOAEL of 71.7 mg/kg bw/day.

It should be realised that the exposure of laboratory animals in the repeated dose dermal toxicity study is not comparable to the human exposure, mainly because the lab-animals are exposed under (semi)occlusion, whereas humans will be exposed to bare skin. This makes it very difficult to use the results from the lab-animals for human risk assessment.

In rats a dose of 71.7 mg/kg bw, at 10% of their body surface; assuming a body surface of area of 400 cm² for a 200 gram rat, corresponds to an area dose of 71.7 mg x 0.2 / 40 cm² = 0.36 mg/cm² . The estimated maximum external human exposure is 4.8 mg at application, and assuming an exposed area of 1 m², this equals an area dose of 4.8/10,000 = 0.00048 mg/cm².

Taking into account the area doses and the NOAEL, and comparing this to the use as described in the GAP and the lack of effects in medical reports, it is not expected that adverse local effects will occur in the unprotected operator and worker after dermal and respiratory exposure to propamocarb-hydrochloride as a result of the application of Infinito by amateur use in potatoes.

Data requirements active substance

Fluopicolide and propamocarb-hydrochlorie:

No additional data requirements are identified.

4.1 Toxicity of the formulated product (IIIA 7.1)

The formulation Infinito does not need to be classified on the basis of its acute oral (LD₅₀ rat > 2500 mg/kg bw), dermal (LD₅₀ rat > 4000 mg/kg bw), and inhalation toxicology (LC₅₀ rat > 3.2 mg/L = max attainable dose).

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

The formulation Infinito is positive in a LLNA test for skin sensitisation and needs to be classified as R43 ‘May cause sensitisation by skin contact’.

4.1.1 Data requirements formulated product

No additional data requirements are identified.

4.2 Dermal absorption (IIIA 7.3)

Fluopicolide

See List of endpoints. The in vitro and in vivo dermal absorption studies were performed with the formulation Infinito. In the original evaluation of Infinito slightly higher values were used. The current values are the final values, set after discussion in the expert meeting.

Propamocarb

See List of Endpoints. It can be assumed that the dermal absorption of propamocarb in the SC formulation Previcur N (evaluated in the DAR) is comparable to the dermal absorption of propamocarb in the SC formulation Infinito. The value in the List of Endpoints is considered to be worst case for Infinito; the new study and evaluation by the RMS is however not considered at this stage based on the calculated risk indices for Infinito using the List of Endpoints values.

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

None of the other formulants raise concerns that have not been addressed in the submitted studies.

4.4 Exposure/risk assessments

Overview of the intended uses

An application has been submitted for the extension of the authorisation of the plant protection product Infinito, a fungicide based on the active substances fluopicolide and propamocarb-hydrochloride.

Infinito is a SC formulation and contains 62.5 g/L fluopicolide and 625 g/L propamocarb-hydrochloride (equivalent to 525.2 g/L propamocarb).

The intended uses are listed under 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

Fluopicolide

Tier 1

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

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

Since the formulation is applied 1-4 times during the period April – September, with an interval of 7 days, a semi-chronic exposure duration is applicable for the operator.

Since fluopicolide is included in Annex I of 91/414/EEC, the semi-chronic EU-AOEL of 0.05 mg/kg bw/day (= 3.15 mg/day for a 63-kg amateur operator), based on the 90-day study in rats is used for the risk assessment (see List of Endpoints).

Exposure/risk

Exposure to fluopicolide during mixing and loading and application of Inifinito 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 fluopicolide and risk assessment for the use of Infinito

	Route	Estimated internal exposure ^a(mg /day)	Systemic EU-AOEL (mg/day)	Risk-index ^b
Manual downward spraying on potatoes (uncovered)
Mixing/ Loading^c/d	Respiratory	<0.01	3.15	<0.01
Mixing/ Loading^c/d	Dermal	<0.01	3.15	<0.01
Application^e	Respiratory	<0.01	3.15	<0.01
Application^e	Dermal	0.13	3.15	0.04
	Total	0.13	3.15	0.04

a Internal exposure was calculated with:

· biological availability via the dermal route: 0.24% (concentrate) and 2.75% (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 (inhalation).

d External exposure is estimated with EUROPOEM (dermal).

e External exposure is estimated with UK POEM.

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

Propamocarb-hydrochloride

Tier 1

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

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

Since the formulation is applied 1-4 times during the period April – September, with an interval of 7 days, a semi-chronic exposure duration is applicable for the operator.

Since propamocarb is included in Annex I of 91/414/EEC, the chronic EU-AOEL of 0.29 mg propamocarb-hydrochloride/kg bw/day (= 18.3 mg/day for a 63-kg amateur operator), based on the 52-week study in rats can be used for the risk assessment (see List of Endpoints). This will result in some overestimation of the real risk.

Exposure/risk

Exposure to propamocarb-hydrochloride during mixing and loading and application of Infinito 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.2 Internal operator exposure to propamocarb-hydrochloride and risk assessment for the use of Infinito

	Route	Estimated internal exposure ^a(mg /day)	Systemic EU-AOEL (mg/day)	Risk-index ^b
Manual downward spraying on potatoes (uncovered)
Mixing/ Loading^c/d	Respiratory	<0.01	18.3	<0.01
Mixing/ Loading^c/d	Dermal	0.19	18.3	0.01
Application^e	Respiratory	0.06	18.3	<0.01
Application^e	Dermal	4.78	18.3	0.26
	Total	5.03	18.3	0.27

a Internal exposure was calculated with:

· biological availability via the dermal route: 10% (concentrate) and 10% (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 (inhalation).

d External exposure is estimated with EUROPOEM (dermal).

e External exposure is estimated with UK POEM.

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

Fluopicolide and propamocarb-hydrochloride

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.

4.4.3 Worker exposure/risk

Fluopicolide and propamocarb-hydrochloride

Shortly after application it is not necessary to perform any re-entry activities during which intensive contact with the treated crop will occur. Therefore no worker exposure is calculated.

4.4.4 Re-entry

Fluopicolide and propamocarb-hydrochloride

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 amateur operator after dermal and respiratory exposure to fluopicolide or propamocarb-hydrochloride as a result of the application of Infinito in potatoes.

Bystander exposure

Based on the risk assessment, it can be concluded that no adverse health effects are expected for the unprotected bystander after dermal and respiratory exposure to fluopicolide or propamocarb-hydrochloride as a result of the application of Infinito in potatoes.

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 potatoes due to exposure to fluopicolide or propamocarb-hydrochloride after the application of Infinito.

These conclusions are also valid for the simultaneous exposure to fluopicolide and propamocarb-hydrochloride (see 4.7).

4.5 Appropriate mammalian toxicology and operator exposure end-points relating to the product and approved uses

See List of Endpoints.

4.6 Data requirements

Based on this evaluation, no additional data requirements are identified.

4.7 Combination toxicology

The formulation Infinito is a mixture of 2 active substances. The combined toxicological effect of these 2 active substances has not been investigated with regard to repeated dose toxicity. However, the critical effects of these two active substances differ considerably, liver hypertrophy for fluopicolide versus vacuolar changes (in the rat specifically in the epithelial cells of the choroids plexus of the brain) for propamocarb-hydrochloride. Therefore, no extra risks are expected for the simultaneous exposure to both substances.

4.8 Mammalian toxicology classification and labelling

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

Fluopicolide

Symbol:

Indication of danger: -

Risk phrases

Propamocarb-hydrochloride

Symbol:

Indication of danger: Harmful

Risk phrases

R43

May cause sensitisation by skin contact.

Proposal for the classification and labelling of the formulation concerning health

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 assessment for the operator, as mentioned above, the following labeling 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:	Xi	Indication of danger:	Irritating
R phrases	R43 (optional based on package size)	May cause sensitisation by skin contact.

S phrases	S2 (optional based on package size)	Keep out of the reach of children.
	S36/37 (optional based on package size)	Wear suitable protective clothing and gloves
Special provisions: DPD-phrases³	-	-

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.

Explanation:
Hazard symbol:	-
Risk phrases:	R43 is optionally assigned since Infinito was positive in an LLNA test. As the contents of the package do not exceed 125 ml, it is not necessary to indicate the R- and S-phrases.
Safety phrases:	S2 is optionally assigned to formulations intended for amateur-use when R43 is assigned. S36/37 is optionally assigned based on R43. As the contents of the package do not exceed 125 ml, it is not necessary to indicate the R- and S-phrases.
Other:	-

Applicant has specified to add the optional R43 en S2 to the label, while S36/37 will not be placed on the label.

5. Residues

List of Endpoints

Fluopicolide

Metabolism in plants (Annex IIA, point 6.1 and 6.7, Annex IIIA, point 8.1 and 8.6)
Plant groups covered	Leafy crops (lettuce), root vegetables (potatoes) and fruit crops (grapes)
Rotational crops	Lettuce, Wheat and Radish
Metabolism in rotational crops similar to metabolism in primary crops?	Yes
Processed commodities	Hydrolysis studies simulating pasteurisation, boiling and sterilisation: Fluopicolide was shown to be stable under these conditions.
Residue pattern in processed commodities similar to residue pattern in raw commodities?	Yes
Plant residue definition for monitoring	Fluopicolide
Plant residue definition for risk assessment	Fluopicolide and metabolite M-01 separately
Conversion factor (monitoring to risk assessment)	None

Metabolism in livestock (Annex IIA, point 6.2 and 6.7, Annex IIIA, point 8.1 and 8.6)
Animals covered	Dairy cattle and hens
Time needed to reach a plateau concentration in milk and eggs	Milk = 4 days Egg = 8 days
Animal residue definition for monitoring	Fluopicolide
Animal residue definition for risk assessment	Fluopicolide and metabolite M-01 separately
Conversion factor (monitoring to risk assessment)	None
Metabolism in rat and ruminant similar (yes/no)	Yes
Fat soluble residue: (yes/no)	No

Residues in succeeding crops (Annex IIA, point 6.6, Annex IIIA, point 8.5)

The rotational crop metabolism study indicated that ‘cold’ rotational crop studies would be required. Therefore, rotational crop studies were carried out in the UK, Germany and France. The studies showed that residues of parent fluopicolide in rotational crops at harvest were below the limit of determination (0.01 mg/kg), with the exception of wheat straw which contained residues of up to 0.12 mg/kg. Therefore, as long as the residue definition for monitoring remains as parent, EU MRLs will not need to be set for rotational crops (EU MRLs are not currently set on straw).

Stability of residues (Annex IIA, point 6 introduction, Annex IIIA, point 8 Introduction)

Freezer storage stability study indicated that residues of fluopicolide, M-01 and M-02 are stable for up to 30 months in grape, potato and wheat grain. Fluopicolide, M-01, M-04 and M-05 are stable in wheat straw for at least 18 months.

For animal products, residues of fluopicolide, M-01 and M-02 are stable for at least 2 months in milk, 4 months in fat and muscle and 9 months in liver and kidney.

Residues from livestock feeding studies (Annex IIA, point 6.4, Annex IIIA, point 8.3)
	Ruminant:	Poultry:	Pig:
	Conditions of requirement of feeding studies
Expected intakes by livestock ³ 0.1 mg/kg diet (dry weight basis) (yes/no - If yes, specify the level)	No	No	No
Potential for accumulation (yes/no):
Metabolism studies indicate potential level of residues ≥ 0.01 mg/kg in edible tissues (yes/no)
	Feeding studies (Specify the feeding rate in cattle and poultry studies considered as relevant) Residue levels in matrices : Mean (max) mg/kg
Muscle
Liver
Kidney
Fat
Milk
Eggs

Processing factors (Annex IIA, point 6.5, Annex IIIA, point 8.4)

Crop/ process/ processed product	Number of studies	Processing factors		Amount transferred (%) (Optional)
Crop/ process/ processed product	Number of studies	Transfer factor	Yield factor	Amount transferred (%) (Optional)
Wine	6	0.4
Must	6	0.5
Raisin	2	4

Propamocarb-hydrochloride

Propamocarb-hydrochloride is an existing active substance/a new active substance, included in Annex I of Directive 91/414/EEC. The final List of Endpoints presented below is taken from the EFSA Scientific Report on propamocarb-hydrochloride (2006) 78; 1-80 (d.d. 12 May 2006), also taking into account the final review report on propamocarb-hydrochloride (SANCO/10057/2006 – final, d.d. 25 April 2007). Where relevant, some additional remarks/information are given in italics.

Metabolism in plants (Annex IIA, point 6.1 and 6.7, Annex IIIA, point 8.1 and 8.6)

Plant groups covered	Leafy crops (spinach and lettuce), fruits (tomatoes and cucumbers) and root vegetables (potatoes).
Rotational crops	Lettuce, radish and wheat.
Plant residue definition for monitoring	Sum of propamocarb and its salts, expressed as propamocarb.
Plant residue definition for risk assessment	Same definition as above.
Conversion factor (monitoring to risk assessment)	Not applicable.

Metabolism in livestock (Annex IIA, point 6.2 and 6.7, Annex IIIA, point 8.1 and 8.6)

Animals covered	A metabolism study was not required. A metabolism study in the cow was however submitted.
Animal residue definition for monitoring	None required or proposed.
Animal residue definition for risk assessment	None required or proposed.
Conversion factor (monitoring to risk assessment)	Not applicable
Metabolism in rat and ruminant similar (yes/no)	Yes
Fat soluble residue: (yes/no)	Non fat soluble.

Residues in succeeding crops (Annex IIA, point 6.6, Annex IIIA, point 8.5)

Information was provided

The studies indicate that residues may be present in crops planted within 30 after the application of propamocarb. The residue pattern in rotational crops is similar to that in primary crops. A recommendation on propamocarb products should indicate that crops should not be sowed or planted on soil within 120 days of the application of propamocarb.

Stability of residues (Annex IIA, point 6 introduction, Annex IIIA, point 8 introduction)

Stability studies were presented.

Propamocarb was found to be stable in lettuce, cucumber, tomato and in Brussels sprouts when stored in a freezer for the duration of the test periods which ranged from 1 to 2 years.

Residues from livestock feeding studies (Annex IIA, point 6.4, Annex IIIA, point 8.3)

Intakes by livestock ³ 0.1 mg/kg diet/day:

Ruminant:

Poultry:

Pig:

No feeding studies required

Processing factors (Annex IIA, point 6.5, Annex IIIA, point 8.4)

Crop/processed crop	Number of studies	Transfer factor	% Transference *
Not applicable	Not applicable

* Calculated on the basis of distribution in the different portions, parts or products as determined through balance studies

Comments on/additions to List of Endpoints

No comments.

5.1 Summary of residue data

Only points that are not covered by the List of Endpoints or that need clarification are discussed below.

5.1.5 Supervised residue trials

Fluopicolide

The GAP-NL in potato involves 4 applications at 0.095 kg a.s./ha with an interval of 7 days and a PHI of 7 days. Residue trials performed within a 25% range from cGAP are acceptable: 4-6 x 0.075-0.125 kg ai/ha, interval 3-7d and PHI 6-8d.

The submitted studies on residue trials in Northern Europe were evaluated in the monograph. During eight trials in potato conducted in 2002 in Northern Europe fluopicolide was sprayed 4 times at a dose of 0.1 kg a.s./ha with an interval of 6-7 days (except for the interval between the first and second treatment in two trials: 8 days). In all 8 trials the residues of fluopicolide <0.01 mg/kg at a PHI of 0 days and 5-7 days. Four additional trials in potato conducted in 2001 in Northern Europe, where fluopicolide was sprayed 3 instead of 4 times at a dose of 0.125 kg a.s./ha with an interval of 5-8 days confirmed the non-residue situation for fluopicolide at all PHIs between 0 and 14 days. In all trials, the residues of metabolites M-01 and M-02 were also determined at a PHI of 7 days and found to be <0.01 mg/kg in all cases. Based on these studies, the MRL may be set at the LOQ of the analytical method (0.01* mg/kg). The EU MRL for potato proposed in the draft monograph was 0.02 mg/kg, based on two detections at 0.01 mg/kg in trials in Southern Europe.

The residue levels selected for risk assessment are presented in table R1.

Table R1: Selected residue levels from trials with Fluopicolide.

Crop

Residue levels selected for MRL setting (mg/kg)

STMR

(mg/kg)

Potato

12 x <0.01

<0.01

Propamocarb-hydrochloride

The GAP-NL in potato involves 4 applications at 0.945 kg a.s./ha with an interval of 7 days and a PHI of 7 days. Residue trials performed within a 25% range from cGAP are acceptable: 4-6 x 0.75-1.25 kg ai/ha, interval 3-7d and PHI 6-8d.

A report was submitted presenting the results of 4 trials in potato conducted in 2002 at 4 locations in Northern Europe where propamocarb-HCl was sprayed 4 times at a dose of 1 kg a.s./ha with an interval of 6-7 days (except for the interval between the first and second treatment in one trial: 8 days). In all 4 trials the residues of propamocarb-HCl were <0.01 mg/kg at a PHI of 5-7 days. Although this information by itself would suggest a non-residue situation, information submitted in the past indicates that residues may be found at levels above the LOQ in potato tubers. In previous evaluations the following trials in potato were described: 8 trials with 14 treatments at 0.48 kg a.s./ha with an interval of 6-8 days, PHI 6-14 days, residues <0.05 mg/kg (6X) and 0.06 mg/kg (2X); 8 trials with 6 treatments at 0.95 kg a.s./ha with an interval of 13-15 days, PHI 5-14 days, residues <0.05 mg/kg (6X) 0.07 mg/kg (1X) and 0.08 mg/k (1X). Although the 16 latter trials do not comply with cGAP-NL, they indicate that trials in two growing seasons would be required for the proposed use to demonstrate a non-residue situation. Further information is not required however, since residues from the proposed use are likely to be very low, and the EU-MRL is 0.5 mg/kg. This MRL covers the proposed use.

The residue levels selected for MRL setting and risk assessment are presented in table R2.

Table R2: Selected residue levels from trials with Propamocarb.

Crop

Residue levels selected for MRL setting (mg/kg)

STMR

(mg/kg)

Potatoes

4x <0.01

<0.01

5.1.6 Residues in succeeding crops

Fluopicolide

Confined rotational crop studies are available. [¹⁴C] phenyl and pyridinyl ring labelled fluopicolide was applied to soil at a rate of 0.4 kg a.i./ha (maximal seasonal application rate for potatoes). Lettuce, wheat and radish were planted after 29, 133 and 365 days of ageing. Translocation of radioactive residues was observed. In crops planted after 29 days of ageing TRR were max. 3 mg/kg in consumable parts and max. 14 mg/ in crop parts used for animal feed. Due to the relatively high stability of fluopicolide in soil, TRR found in crops after 365 days of ageing were still max. 0.6 mg/kg in consumable parts and max. 2 mg/kg in crop parts used for animal feed.

Metabolism was found to be similar, but more extensive as in primary crops. In lettuce, radish tops and radish roots fluopicolide, M-01 and M-02 were identified as main components of the radioactive residues. Additionally M-05 and M-09 were found in some of the matrices. The main components of radioactive residues in wheat grain, forage and straw were fluopicolide, M-01, M-02, M-04 and M-05. Low concentrations of M-06, M-08 and M-09 were identified in some of the samples.

From the metabolites identified in rotational crops, M-05, M-08 and M-09 were not found in the rat metabolism studies. However, they are regarded as less toxic as fluopicolide. Therefore, they were not included in the residue definition for risk assessment.

Nine field trials on rotational crops have been submitted. After the harvest of potatoes which were treated with four foliar applications of fluopicolide at a rate of 0.1 kg a.i./ha (N rate), winter and spring wheat, beans and cabbage were planted into the soil after 28-227 days of ageing. Samples were analysed for fluopicolide, M-01 and M-02, wheat samples additionally for M-04 and M-05. Fluopicolide was below the LOQ (0.01 mg/kg) in crops harvested at maturity with the exception of wheat straw which contained up to 0.12 mg/kg. M-01 was found in quantifiable concentrations in cabbage (max. 0.04 mg/kg) and wheat straw (max. 0.03 mg/kg). Low levels (all below 0.1 mg/kg) of M-02, M-04 and M-05 were found in some samples of wheat grain and straw. On the basis of the residue trials on rotational crops, levels of fluopicolide (proposed residue definition for monitoring for plant matrices) below the LOQ are expected in crop parts intended for the human consumption.

Propamocarb-hydrochloride

See List of Endpoints.

5.1.7 Residues from livestock feeding studies

Fluopicolide

In the theoretical intake assessment for dairy cattle/beef cattle/poultry/pigs it was shown that a livestock feeding study does not need to be provided, as the estimated intake is less than 0.1 mg/kg feed (dry weight).

Propamocarb-hydrochloride

5.1.8 Processing factors

Fluopicolide

Studies are not necessary as the total theoretical daily intake (TMDI) is less than 10% of the ADI.

Propamocarb-hydrochloride

Studies are not necessary as the total theoretical daily intake (TMDI) is less than 10% of the ADI.

5.1.9 Calculation of the ADI and the ARfD

Fluopicolide

Calculation of the ADI

The ADI is based on the NOAEL of 8.0 mg/kg bw/d in the 78-week dietary study in mice, supported by the 2-year rat study. Application of a safety factor for inter- and intraspecies differences of 100 results in an ADI of 0.08 mg/kg bw/day (see the List of Endpoints for mammalian toxicology).

Calculation of the ARfD

The ARfD is based on the NOAEL of 18 mg/kg bw/d in the 28-day dietary study in rats and the rabbit developmental study. Application of a safety factor for inter- and intraspecies differences of 100 results in an ARfD of 0.18 mg/kg bw/day (see the List of Endpoints for mammalian toxicology).

Metabolite M01

Calculation of the ADI

The ADI is based on the NOAEL of 5.0 mg/kg bw/d in the 2-year rat and dog studies. Application of a safety factor for inter- and intraspecies differences of 100 results in an ADI of 0.05 mg/kg bw/day (see the List of Endpoints for mammalian toxicology).

Calculation of the ARfD

The ARfD is based on the NOAEL of 30 mg/kg bw/d in the rabbit developmental study. Application of a safety factor for inter- and intraspecies differences of 100 results in an ARfD of 0.3 mg/kg bw/day (see the List of Endpoints for mammalian toxicology).

Propamocarb-hydrochloride

Calculation of the ADI

The ADI is based on the NOAEL of 29 mg/kg bw/d in the 52-week dietary study in rats. Application of a safety factor for inter- and intraspecies differences of 100 results in an ADI of 0.29 mg/kg bw/day (see the List of Endpoints for mammalian toxicology).

Calculation of the ARfD

The ARfD is based on the NOAEL of 100 mg/kg bw/d in the 28-day rat study (gavage). Application of a safety factor for inter- and intraspecies differences of 100 results in an ARfD of 1 mg/kg bw/day (see the List of Endpoints for mammalian toxicology).

5.2 Maximum Residue Levels

Fluopicolide

EU-MRLs are present in Annex IIIa of Regulation (EC) 396/2005.

The product complies with the MRL Regulation. Notification of a MRL is not necessary.

Propamocarb-hydrochloride

EU-MRLs are present in Annex IIIa of Regulation (EC) 396/2005.

The product complies with the MRL Regulation. Notification of a MRL is not necessary.

5.3 Consumer risk assessment

Fluopicolide

Risk assessment for chronic exposure through diet

A calculation of the Theoretical Maximum Daily Intake (TMDI) was carried out using EFSA PRIMo rev. 2.0, containing all available Member State diets, and the EU-MRLs. The maximum TMDI is 11.0 % of the ADI for FR all population. The TMDI is 3.4 % and 4.2 % of the ADI for the Dutch general population and Dutch children ages 1-6, respectively.

Risk assessment for acute exposure through diet

A calculation of the Estimated Short Term Intake (ESTI) was carried out using EFSA PRIMo rev. 2.0 and the EU MRL of 0.02 mg/kg for potatoes. The highest percentage of the ESTI is 1.7 % of the ARfD for the UK infant. ESTI values for the other commodities in all other consumer diets are all lower.

Metabolite M01

Risk assessment for chronic exposure through diet

A calculation of the Theoretical Maximum Daily Intake (TMDI) was carried out using EFSA PRIMo rev. 2.0, containing all available Member State diets, and the residue values of grapes (proposed HR of 0.05 mg/kg in the DAR), potatoes (LOQ of 0.01 mg/kg), and rotational crops (for leaf vegetables, head and leaf brassica and herbs at the highest residue level for cabbage of 0.04 mg/kg, for other root and tuber vegetables and cereals at the LOQ of 0.01 mg). The maximum TMDI is 0.6 % of the ADI for the WHO cluster B diet.

Risk assessment for acute exposure through diet

A calculation of the Estimated Short Term Intake (ESTI) was carried out using EFSA PRIMo rev. 2.0 and the residue values of potatoes (LOQ of 0.01 mg/kg), and rotational crops (for leaf vegetables, head and leaf brassica and herbs at the highest residue level for cabbage of 0.04 mg/kg, for other root and tuber vegetables and cereals at the LOQ of 0.01 mg). The highest percentage of the ESTI is 1 % of the ARfD for the NL child for scarole. ESTI values for the other commodities in all other consumer diets are all lower.

Propamocarb-hydrochloride

Risk assessment for chronic exposure through diet

A calculation of the Theoretical Maximum Daily Intake (TMDI) was carried out using EFSA PRIMo rev. 2.0, containing all available Member State diets, and the EU-MRLs. The maximum TMDI is 67.2 % of the ADI for DE child. The TMDI is 18.7 % and 48.3 % of the ADI for the Dutch general population and Dutch children ages 1-6, respectively.

Risk assessment for acute exposure through diet

A calculation of the Estimated Short Term Intake (ESTI) was carried out using EFSA PRIMo rev. 2.0 and the EU MRL of 0.5 mg/kg for potatoes. The highest percentage of the ESTI is 7.7 % of the ARfD for the UK infant. ESTI values for the other commodities in all other consumer diets are all lower.

Conclusion

Based on the assessment for residues, no risk for the consumer due to the exposure to fluopicolide and propamocarb-hydrochloride is currently expected.

The product complies with the Uniform Principles.

5.4 Data requirements

None.

6. Environmental fate and behaviour

Fluopicolide is a new activ substance for the EU included in Annex I (RMS UK). The LoEP is taken from the EFSA scientific report (4 June 2009).

Propamocarb-hydrochloride is an existing active substance included in Annex I as propamocarb (RMS: Ireland), inclusion directive 7/25/EC, inclusion date 1/10/2007. Furthermore, an EFSA risk assessment is available (EFSA Scientific Report (2006) 78). The LoEP is taken from the EFSA scientific report (May 2006). Notifiers are Bayer and Agriphar.

In the inclusion directive it is mentioned: With relevance to fate and behaviour, Member States must pay particular attention to:

the protection of surface and groundwater in vulnerable zones

List of Endpoints Fate/behaviour

Fluopicolide

The LoEP is taken from the EFSA scientific report (EFSA Scientific Report (2009) 299).

NL commented on the DAR. Where relevant, some additional remarks/information are given in italics. Some fate studies have additionally been evaluated by the RIVM in report 10904. The results of this evaluation are also mentioned within the LoEP and used in the risk assessment when appropriate.

Route of degradation (aerobic) in soil (Annex IIA, point 7.1.1.1.1)

Mineralization after 100 days ‡

0 - 0.2% AR at 94-98 days in 3 soils (pyridinyl label)

0 - 2.0% AR at 94-98 days in 5 soils (benzoyl label)

sterile conditions: not detected

Non-extractable residues after 100 days ‡

9.2 - 16.2% AR at 94-116 days in 3 soils (pyridinyl label)

4.0 - 12.0% AR at 94-120 days in 5 soils (benzoyl label)

sterile conditions: 3.1 – 8.0% AR at 120 days

Metabolites requiring further consideration ‡
- name and/or code, % of applied (range and maximum)

M-01: range of max. formed 4.8-25.0% AR at 94-120 days in 5 soils (benzoyl label), detected to a maximum of 40.2% at day 369 in one study but this is over the 120 day acceptable limit for laboratory studies.

M-02: range of max. formed 1.5-7.3% AR at 42-116 days in 3 soils (pyridinyl label).

M-03: range of max. formed 1.4-10.6% AR at 77-120 days in 5 soils (benzoyl label). Range of max. formed 1.5-7.8% AR at 77-120 days in 3 soils (pyridinyl label). Highest levels found in acid soils.

Route of degradation in soil - Supplemental studies (Annex IIA, point 7.1.1.1.2)

Anaerobic degradation ‡

Mineralization after 100 days

Not detected after 120 d (pyridinyl label) (n= 1)

0.1% AR after 120 d, (benzoyl label) (n= 1)

Non-extractable residues after 100 days

4.4% AR after 120 d (pyridinyl label) (n= 1)

4.5% AR after 120 d, (benzoyl label) (n= 1)

Metabolites that may require further consideration for risk assessment - name and/or code, % of applied (range and maximum)

M-01 (max 2.1% AR at 120 days) (n = 1)

M-02 (max 8.9% AR at 120 days) (n = 1)

Soil photolysis ‡

Metabolites that may require further consideration for risk assessment - name and/or code, % of applied (range and maximum)

Continuous irradiation, equivalent to 4x the average daily irradiation at 55˚N, 15 days duration.

M-01 max 8.6%AR at 15 days (n=1)

M-02 max 2.6%AR at 10 days (n=1)

Rate of degradation in soil (Annex IIA, point 7.1.1.2, Annex IIIA, point 9.1.1)
Laboratory studies ‡
Fluopicolide	Aerobic conditions
Soil type	X^{^[1]}	pH (CaCl₂)	t. ^oC / % MWHC	DT₅₀ /DT₉₀ (d)	DT₅₀ (d) 20 °C pF2/10kPa	St. (r²)	Method of calculation
Sandy loam		7.5	20/pF2-2.5	282/936	277/920	0.997/0.998	SFO, mean of 2 labels
Clay loam		5.9	25/75% of ⅓ bar	276/917	276/917	0.983/0.988	SFO, mean of 2 labels
Loamy sand		5.7	25/75% of ⅓ bar	329/1093	300/997	0.988/0.991	SFO, mean of 2 labels
Silty clay loam		7.4	20/pF2	194/644	194/644	-	SFO, single label position
Loamy sand		4.9	20/pF2	266/884	266/884	-	SFO, single label position
Clay loam		5.6	20/pF2.5	411/1365	333/1106	0.991/0.997	SFO, mean of 2 labels
Sandy loam		7.2	10/40%	667/2216		0.998	SFO, pyridinyl label only
Geometric mean (excludes 10˚C study)					271/900

Note: field derived DT50 values used in FOCUS modelling

M-01 (BAM)	Aerobic conditions, metabolite applied as starting substance
Soil type	X¹	pH (H₂O)	t. ^oC / % MWHC	DT₅₀/ DT₉₀ (d)	f. f. k_dp/k_f	DT₅₀ (d) 20 °C pF2/10kPa	St. (r²)	Method of calculation
Sandy loam		4.8	25/75% of ⅓ bar	1831/6083	-	1848/6139	0.775	SFO
Sandy loam		7.7	25/75% of ⅓ bar	557/1850	-	808/2684	0.874	SFO
Geometric mean/median				N/A	-	N/A

N/A = not appropriate, i.e. due to small database; note: field derived DT50 values used in FOCUS modelling

M-02	Aerobic conditions, metabolite applied as starting substance
Soil type	X¹	pH (CaCl₂)	t. ^oC / % MWHC	DT₅₀/ DT₉₀ (d)	f. f. k_dp/k_f	DT₅₀ (d) 20 °C pF2/10kPa	St. (r²)	Method of calculation
Sandy loam		7.2	20/40-50%	4.5/15	-	3	0.99	SFO
Loamy sand		5.4	20/40-50%	3.2/10.6	-	2.5	0.98	SFO
Silty clay loam		7.5	20/40-50%	4.5/15	-	3	0.99	SFO
Geometric mean				4.0/13.3	-	2.8*

* used in FOCUSgw modelling

M-03	Aerobic conditions, metabolite applied as starting substance
Soil type	X¹	pH (CaCl₂)	t. ^oC / % MWHC	DT₅₀/ DT₉₀ (d)	f. f. k_dp/k_f	DT₅₀ (d) 20 °C pF2/10kPa	St. (r²)	Method of calculation
Sandy loam		5.4	20/40%	2.2/7.3	-	1.7	0.99	SFO
Loamy sand		4.9	20/40%	5.0/16.6	-	4.7	0.96	SFO
Sandy loam		7.2	20/40%	0.1/0.3	-	0.1	1.0	SFO
Silt loam		7.1	20/40%	0.1/0.3	-	0.09*	1.0	SFO
Geometric mean				0.6/2		0.5

*FOCUSgw modelling DT50 of 0.09 days for scenarios with pH>6 and 55.5 days for scenarios with pH<6 (from field studies)

M-05	Aerobic conditions, metabolite applied as starting substance
Soil type	X¹	pH	t. ^oC / % MWHC	DT₅₀/ DT₉₀ (d)	f. f. k_dp/k_f	DT₅₀ (d) 20 °C pF2/10kPa	St. (r²)	Method of calculation
Sandy loam		7.2	20/40-45%	60/199	-	41	0.99	SFO
Loamy sand		5.4	20/40-45%	130/432	-	100	0.96	SFO
Silty clay loam		7.5	20/40-45%	34/113	-	22	0.98	SFO
Geometric mean				64/213	-	45
	Aerobic conditions, metabolite M-02 applied as starting substance
Sandy loam		7.2	20/40-50%	31	0.256	20.7		SFO
Loamy sand		5.4	20/40-50%	118	0.184	90.7		SFO
Silty clay loam		7.5	20/40-50%	53	0.17	35.2		SFO
Geometric mean				58	0.203*	40.4
Geometric mean of all M-05 normalised DT50 values for modelling						42.6

* arithmetic mean used as some formation fractions were 0 in modelling of M-02 study; geometric mean cannot be calculated where 0 is present in the range of values

M-10	Aerobic conditions, metabolite applied as starting substance
Soil type	X¹	pH	t. ^oC / % MWHC	DT₅₀/ DT₉₀ (d)	f. f. k_dp/k_f	DT₅₀ (d) 20 °C pF2/10kPa	St. (r²)	Method of calculation
Sandy loam		7.2	20/40-45%	253/840	-	194	0.89	SFO
Loamy sand		5.4	20/40-45%	36/120	-	24	0.95	SFO
Silty clay loam		7.5	20/40-45%	24/80	-	16	0.96	SFO
Geometric mean				60/199		42
	Aerobic conditions, metabolite M-02 applied as starting substance
Sandy loam		7.2	20/40-50%	4.5/	0.175	3.0		SFO
Loamy sand		5.4	20/40-50%	307/	0.036	236		SFO
Silty clay loam		7.5	20/40-50%	9.7/	0.074	6.4		SFO
Geometric mean/median				24/79	0.095*	16.5
Geometric mean of all M-10 normalised DT50 values for modelling						26.4

* arithmetic mean used as some formation fractions were 0 in modelling of M-02 study; geometric mean cannot be calculated where 0 is present in the range of values

M-14	Aerobic conditions, metabolite applied as starting substance
Soil type	X¹	pH	t. ^oC / % MWHC	DT₅₀/ DT₉₀ (d)	f. f. k_dp/k_f	DT₅₀ (d) 20 °C pF2/10kPa	St. (r²)	Method of calculation
Sandy loam		7.2	20/40-45%	8/27	-	6.3	1.0	SFO
Loamy sand		5.4	20/40-45%	5/17	-	3.3	1.0	SFO
Silty clay loam		7.5	20/40-45%	6/20	-	3.8	1.0	SFO
Geometric mean					-	4.3
	Aerobic conditions, metabolite M-02 applied as starting substance
Sandy loam		7.2	20/40-50%	7.9/26	0.384	5.3		SFO
Loamy sand		5.4	20/40-50%	-	0	-		SFO
Silty clay loam		7.5	20/40-50%	13.7/46	0.371	9.1		SFO
Geometric mean				10.4/35	0.384*	6.9
Geometric mean of all M-10 normalised DT50 values for modelling						5.2

* not applicable as some formation fractions were 0 in modelling of M-02 study. Worst case 0.384 was agreed by PRAPeR 37 as end point for the metabolite M14.

M-11/12	Aerobic conditions, metabolite M-02 applied as starting substance
Soil type	X¹	pH	t. ^oC / % MWHC	DT₅₀/ DT₉₀ (d)	f. f. k_dp/k_f	DT₅₀ (d) 20 °C pF2/10kPa	St. (r²)	Method of calculation

Sandy loam		7.2	20/40-50%	41/136	0.013	27.3		SFO
Loamy sand		5.4	20/40-50%	86.1/286	0.127	66.2		SFO
Silty clay loam		7.5	20/40-50%	38.5/128	0.019	25.8		SFO
Geometric mean				51.4/171	0.053*	36

* arithmetic mean used

M-13	Aerobic conditions, metabolite M-02 applied as starting substance
Soil type	X¹	pH	t. ^oC / % MWHC	DT₅₀/ DT₉₀ (d)	f. f. k_dp/k_f	DT₅₀ (d) 20 °C pF2/10kPa	St. (r²)	Method of calculation

Sandy loam		7.2	20/40-50%	10.9/36	0.085	7.3		SFO
Loamy sand		5.4	20/40-50%	43/143	0.03	33.1		SFO
Silty clay loam		7.5	20/40-50%	10.3/34	0.07	6.9		SFO
Geometric mean				16.9/56	0.062*	11.8

* arithmetic mean used

Field studies ‡
Fluopicolide	Aerobic conditions
Soil type (indicate if bare or cropped soil was used).	Location (country or USA state).	X¹	pH	Depth (cm)	DT₅₀ (d) actual	DT₉₀(d) actual	St. (r², chi²)	DT₅₀ (d) Norm.	Method of calculation
Loamy sand, bare	Germany (Philippsburg)		6.4	50	99	1184	0.879, 15.9	177.7	Actual: HS, k1=0.0206 d^-1, k2 0.00148 d^-1, bp 28.6 d Norm: SFO
Clay, bare	Germany (Rodelsee)		7.3	50	132	863	0.940, 12.2	123.3	Actual: HS, k1=0.0309 d^-1, k2 0.0022 d^-1, bp 14.0 d Norm: SFO
Loamy sand, bare	Germany (Huntlosen)		4.9	50	172	1000	0.789, 14.0	117.5	Actual: HS, k1=0.0440 d^-1, k2 0.0019 d^-1, bp 8.5 d Norm: SFO
Sandy silt loam, bare	N France (Appilly)		7.1	50	104	1134	0.891, 14.9	161.2	Actual: HS, k1=0.0067 d^-1, k2 0.0014 d^-1, bp 136.0 d Norm: SFO
Sandy loam, bare	Spain (Valencia)		7.3	50	50	973	0.953, 11.8	223.6	Actual: HS, k1=0.0138 d^-1, k2 0.00163 d^-1, bp 60.4 d Norm: SFO
Sandy silt loam, bare	S France (Senas Yr 1)		7.6	50	115	619	0.832, 8.7	77.0	Actual: HS, k1=0.0608 d^-1, k2 0.0032 d^-1, bp 5.6 d Norm: SFO
Sandy silt loam, bare	S France (Senas Yr 2)		7.3	50	58	679	0.928, 12.7	77.0	Actual: HS, k1=0.0119 d^-1, k2 0.00242 d^-1, bp 69.8 d Norm: SFO
Geometric mean/median								138.8

HS = Hockey stick; BP = break point in days

Note: RMS UK calculated SFO dissipation rates resulting in inferior fits compared to Applicant ‘best fit’ approach listed above. However, for simplistic PECsoil approaches, a worst-case SFO DT50 of 290 days (r² = 0.818) is proposed on the basis of the following RMS calculated SFO values:

Soil type (indicate if bare or cropped soil was used).	Location (country or USA state).	DT₅₀ (d) actual	St. (r²)
Loamy sand, bare	Germany (Philippsburg)	248	0.727
Clay, bare	Germany (Rodelsee)	253	0.818
Loamy sand, bare	Germany (Huntlosen)	290	0.818
Sandy silt loam, bare	N France (Appilly)	187	0.884
Sandy loam, bare	Spain (Valencia)	174	0.817
Sandy silt loam, bare	S France (Senas Yr 1)	174	0.931
Sandy silt loam, bare	S France (Senas Yr 2)	133	0.826

M-01	Aerobic conditions
Soil type	Location	pH	Depth (cm)	DT₅₀ (d) actual	DT₉₀ (d) actual	St. (r2)	DT₅₀ (d) Norm.	Method of calculation
Loamy sand, bare	Germany	6.4	50	120	399	0.881	144.4	Actual: SFO from peak Norm: SFO¹
Clay, bare	Germany	7.3	50	315	1046	0.873	73.0	Actual: SFO from peak Norm: SFO¹
Loamy sand, bare	Germany	4.9	50	257 (unreliable, 4 data points only)	854		141.5	Actual: SFO from peak Norm: SFO¹
Sandy silt loam, bare	N France	7.1	50	186	618	0.930	173.3	Actual: SFO from peak Norm: SFO¹
Sandy loam, bare	Spain	7.3	50	-	-		256.7	Actual: max too close to end of study Norm: SFO¹
Sandy silt loam, bare	S France	7.6	50	267	887	0.800	136.6	Actual: SFO from peak Norm: SFO¹
Sandy silt loam, bare	S France	7.3	50	120	399	0.881	81.5	Actual: SFO from peak Norm: SFO¹
Geometric mean							137.7*

* for calculation of geomean, the two S France results were meaned before calculating overall mean.. This value used in FOCUS exposure modelling

¹ represents degradation rate only for M-01, not dissipation rate

For simplistic PECsoil calculations for M-01, it proposed that the longest dissipation DT50 of 315 days is used with maximum observed formation of 14.6% wt/wt.

M-03: a SFO normalised field degradation DT50 was only calculable for this metabolite at one German loamy sand site with pH 4.9; this was 55.5 days from the Huntlosen, Germany site.

pH dependence ‡
(yes / no) (if yes type of dependence)

No pH dependence for fluopicolide or M-01. Possibility of pH dependence of degradation for M-03, slower degradation at acid pH.

Soil accumulation and plateau concentration ‡

Three sites

Senas, S France, applications made 1999 – 2002; application at 500 g a.s./ha each year

Appilly, N France, applications made 2000 – 2004; application at 400 g/ha each year

Philippsburg, Germany, applications made 2000 – 2004; application at 400 g a.s./ha each year.

Location	Plateau concentration	Fluopicolide (mg/kg)		M-01 (mg/kg)
Location	Plateau concentration	0-10 cm	0-20 cm	0-10 cm	0-20 cm
Senas	High¹	0.354	0.192	0.047	0.030
Senas	Low²	0.082	0.046	0.015	0.016
Appilly	High	0.387	0.197	0.036	0.026
Appilly	Low	0.144	0.080	0.034	0.025
Philippsburg	High	0.341	0.191	0.070	0.042
Philippsburg	Low	0.094	0.064	0.024	0.021

¹ maximum of the high values of the “saw teeth” curve
² maximum of the low values of the “saw teeth” curve

Laboratory studies ‡
Fluopicolide	Anaerobic conditions
Soil type	X^{^[2]}	pH (CaCL₂)	t. ^oC / % MWHC	DT₅₀ / DT₉₀ (d)	DT₅₀ (d) 20 °C pF2/10kPa	St. (r²)	Method of calculation
Sandy loam		7.5	20/flooded	424/1409	-	0.998	SFO, whole system, mean of 2 labels

Laboratory studies ‡
Fluopicolide	Soil photolysis
Soil type	X^{^[3]}	pH (CaCL₂)	t. ^oC / % MWHC/illumination	DT₅₀ / DT₉₀ (d)	DT₅₀ (d) 20 °C pF2/10kPa	St. (r²)	Method of calculation
Sandy loam		7.3-7.4	20/air dry/15 days continuous, equiv. 30 days natural summer sunlight in N EU (55ºN)*	40.4/~~134~~ 34 experiment-al days Dark control DT50 103 d/no degradation (Applicant’s calculation) 61 experimental days Dark control DT50 198d/ no degradation (RMS calculation)	-	0.998	SFO, mean of 2 labels

* Following expert meeting discussion, an assessment was made of the contribution of photolysis to degradation in soil at a range of European locations/latitudes from Athens, Greece (36.03ºN) to Dundee, UK (56.26ºN) based on example solar radiation in June for these locations; values for Tunisia have been ignored. Using the applicants calculated photolytic DT50 for the studies, environmental DT50 values were in the range 89 – 198 days.

Soil adsorption/desorption (Annex IIA, point 7.1.2)
Fluopicolide ‡
Soil Type	OC %	Soil pH (CaCl₂)	Kd (mL/g)	Koc (mL/g)	Kf (mL/g)	Kfoc (mL/g)	1/n
Top soils
Sand	0.5	4.7			1.42	283	0.924
Sandy loam	2.21	7.5			7.53	341	0.929
Silty clay loam	0.9	7.4			3.20	356	0.905
Loamy sand	1.3	5.7			4.54	349	0.929
Sandy loam	0.6	6.3			1.49	248	0.841
Loamy sand	1.6	5.3			9.27	580	0.953
Clay	1.5	7.0			2.59	172	0.859
Silty clay loam	1.5	7.6			3.59	239	0.882
Arithmetic mean of top soils					4.20	321.1	0.9028
Sediment
Clay loam	2.07	4.5			7.73	373	0.926
Sub soils
Sand	0.2	6.2			0.21	106	0.931
Loamy sand	0.2	6.2			0.17	83	0.951
pH dependence, Yes or No			No pH dependence

M-01 ‡
Soil Type	OC %	Soil pH (H₂O)	Kd (mL/g)	Koc (mL/g)	Kf (mL/g)	Kfoc (mL/g)	1/n
Sandy loam	0.9	4.8			0.3588	39.9	0.97
Sandy loam	5.7	7.7			1.761	31	0.8085
Sand	1.4	6.3			0.529	38	0.9163
Sand	4.2	4.9			1.89	45	0.9125
Clay loam	0.4	6.6			0.208	51	0.9718
Arithmetic mean/median					0.95	40.98	0.92
pH dependence (yes or no)			No pH dependence

M-02 ‡
Soil Type	OC %	Soil pH (CaCl₂)	Kd (mL/g)	Koc (mL/g)	Kf (mL/g)	Kfoc (mL/g)	1/n
Sandy loam	2.6	7.2			0.029	1.1	0.725
Loamy sand	1.1	5.4			0.116	10.5	0.887
Silty clay loam	1.3	7.5			0.082	6.3	0.709
Arithmetic mean/median					0.076	6.0	0.774
pH dependence (yes or no)			No pH dependence

M-03 ‡
Soil Type	OC %	Soil pH (CaCl₂)	Kd (mL/g)	Koc (mL/g)	Kf (mL/g)	Kfoc (mL/g)	1/n
Sandy loam	3.5	4.1			2.86	82	0.961
Loamy sand	1.7	4.5			2.26	133	1.012
Loamy sand	1.1	5.4			1.23	112	0.939
Arithmetic mean/median					2.12	109	0.971
pH dependence (yes or no)			No pH dependence at acid pH. M-03 not tested at more alkaline pH due to instability at such pH.

M-05 ‡
Soil Type	OC %	Soil pH (CaCl₂)	Kd (mL/g)	Koc (mL/g)	Kf (mL/g)	Kfoc (mL/g)	1/n
Sandy loam	2.6	7.2			0.294	11	0.883
Loamy sand	1.1	5.4			0.544	49	0.954
Clay loam	1.3	7.5			0.218	17	0.918
Arithmetic mean/median					0.352	26	0.918
pH dependence (yes or no)			No pH dependence

M-10 ‡
Soil Type	OC %	Soil pH (CaCl₂)	Kd (mL/g)	Koc (mL/g)	Kf (mL/g)	Kfoc (mL/g)	1/n
Sandy loam	2.6	7.2	0.003	0.07
Loamy sand	1.1	5.4	0.09	8.24
Clay loam	1.3	7.5	0.14	10.66
Arithmetic mean/median			0.08	6.3
pH dependence (yes or no)			No pH dependence

M-11, M-12, M-13: Koc value of 0 assumed as a worse-case; 1/n 0.9 assumed as default.

M-14: Koc 19.2 from HPLC determination; 1/n 0.9 assumed as default.

Mobility in soil (Annex IIA, point 7.1.3, Annex IIIA, point 9.1.2)
Column leaching ‡	Not submitted, not required

Aged residues leaching ‡	Not submitted, not required

Lysimeter/ field leaching studies ‡

Location: Germany

Study type (e.g. lysimeter, field): lysimeter

Soil properties: loamy sand, pH = 5.2, OC= 1.1, MWHC = NA

Dates of application : Lysimeter 32 – 27/5/99, 17/6/99, 20/7/99, 30/7/99; Lysimeter 33 – first year, 27/5/99, 17/6/99, 20/7/99, 30/7/99, second year 6/5/00, 19/5/00, 23/6/00, 10/7/00

Crop : /Interception estimated: Potato/applied post emergence, interception not quantified for whole lysimeter surface area but interception did occur.

Number of applications: Lysimeter 32, 1 year, 4 applications per year; Lysimeter 33, 2 years, 4 applications per year.

Duration. 3 years

Application rate: Lysimeter 32, 422.2 g a.s./ha/year; Lysimeter 33, 429.5 g a.s./ha/year 1, 412.0 g a.s./ha/year 2. Pyridinyl labelling position used

Average annual rainfall (mm): see below

Average annual leachate volume (mm):see below

% radioactivity in leachate (maximum/year): Lysimeter 32, 1.83 – 2.67 % AR; Lysimeter 33, 1.04 – 1.57 % AR

Individual annual maximum concentrations (e.g. 1^st, 2^nd, 3^rd yr): see below.

Individual annual average concentrations (e.g. 1^st, 2^nd, 3^rd yr): see below.

Amount of radioactivity in the soils at the end of the study = Lysimeter 32, 43.12 % AR; 22.7% AR extractable in top 20cm, virtually all as parent; Lysimeter 33, 48.92 % AR; 28.9% AR extractable in top 20cm, virtually all as parent.

M-01 not detected as benzoyl labelling position NOT used

Annual average concentration of metabolites in lysimeter leachate over 3 years.

	Year 1		Year 2		Year 3
	L32	L33	L32	L33	L32	L33
Total rainfall (mm)	666.1		825.7		928.0
Total rainfall + irrigation (mm)	850.1	830.1	875.7		1008.0
Total leachate volume (mm)	335.6	360.3	374.2	333.5	469.2*	374.9
Fluopicolide (µg/l)	<LOD	<LOD	<LOD	<LOD	<LOD	<LOD
M-01 (µg/l)	-	-	-	-	-	-
M-05 (µg/l)	0.37	0.31	0.33	0.46	0.31	0.90
M-10 (µg/l)	0.83	0.68	0.07	0.23	0.10	0.29
M-11 (µg/l)⁺	0.55	0.47	0.45	0.47	0.30	0.34
M-12 (µg/l)⁺	0.36	0.31	0.30	0.31	0.20	0.23
M-13 (µg/l)	0.05	0.04	0.08	0.08	0.07	0.14
M-14 (µg/l)	0.04	0.05	0.08	0.06	0.08	0.19
M-15 (µg/l)	0.03	<LOD	0.04	0.09	<LOQ	0.10¹
M-16 (µg/l)	0.03	<LOD	0.04	0.06	<LOD	0.08
M54	0.02	<LOD	0.02	0.03	<LOD	<LOQ
P6A	0.02	<LOD	0.02	0.03	<LOD	<LOQ
P6	<LOD	<LOD	0.04	0.03	0.06	0.07
M3	0.02	<LOD	0.03	0.02	0.02	0.04
M29	0.02	0.09	<LOD	<LOQ	<LOD	<LOQ
Unresolved	0.15	0.04	0.03	0.00	0.04	0.16

*52.1 litres collected in one day (10/07/01) – Applicant proposes that this is due to preferential flow during heavy thunderstorms.

⁺two isomers of the same metabolite

LOD = Limit of detection (0.004 to 0.014 µg/l)

LOQ = Limit of quantification (0.008 to 0.028 µg/l)

¹ = rounded to 0.10 µg/l from 0.095 µg/l

Individual annual max concentration in leachate samples (only results >0.1 µg/l given)

	Year 1		Year 2		Year 3
	L32	L33	L32	L33	L32	L33
Total rainfall (mm)	666.1		825.7		928.0
Total rainfall + irrigation (mm)	850.1	830.1	875.7		1008.0
Total leachate volume (mm)	335.6	360.3	374.2	333.5	469.2*	374.9
Fluopicolide (µg/l)	<LOD	0.761	<LOD	<LOD	<LOD	<LOD
M-01 (µg/l)	-	-	-	-	-	-
M-05 (µg/l)			0.823	1.903	0.679	2.256
M-10 (µg/l)			0.187	0.629	0.224	0.609
M-11 (µg/l)⁺			0.916	1.082	0.699	0.721
M-12 (µg/l)⁺			0.611	0.721	0.466	0.480
M-13 (µg/l)			0.163	0.317	0.160	0.344
M-14 (µg/l)			0.156	0.197	0.217	0.418
M-15 (µg/l)				0.216		0.134
M-16 (µg/l)				0.118		0.127
P6A					0.102
P6						0.202

Results for metabolites in year 1 not available

Non RL field leaching study (Germany), 400g/ha fluopicolide applied in year 1 to lettuce, leachate collected for 3 years using suction samplers installed at 5 different depths down to 150 cm. Range of maximum annual average concentration over the three years:

Fluopicolide: 30 cm 1.145-1.688 µg/l, 50 cm 0.078-0.173 µg/l, 85 cm <LOQ-0.081 µg/l, no residues found above LOQ (0.075µg/l) below this depth during remainder of study.

M-01: 30 cm 2.930-6.691 µg/l, 50 cm 3.257-5.764 µg/l, 85 cm 0.845-4.361 µg/l, 120 cm 0.282-2.928 µg/l, 150 cm 0.085-2.415 µg/l.

M-02: 30 cm 0.054-0.100 µg/l, 50 cm <LOQ-0.058 µg/l, no residues found above LOQ (0.075µg/l) below this depth during remainder of study.

M-03: No residues found above LOQ (0.075µg/l) throughout study.

PEC (soil) (Annex IIIA, point 9.1.3)

Parent

Method of calculation

Potato (based on applicant calculation): accumulation calculated using FOCUS-PELMO with Hamburg and Thiva scenarios. Soil bulk density 1.5 g/cm³. GAP 4 x 100 g/ha, 2 applications with 50% interception, 2 applications with 80% interception, 5 day intervals, application once every two years. Fluopicolide DT₅₀ = 200.7 days, M-01 DT50 215.0 days (both values 90^th percentile worst case DT50 at 20˚C and pF2 calculated from field studies). Incorporation to 20 cm for potato, peak concentration adjusted for incorporation in 5/10 cm following final application.

Vines (based on RMS calculation): accumulation calculated with simplistic spreadsheet method. Soil bulk density 1.5 g/cm³. GAP 3 x 133 g/ha, 70% interception, 10 day intervals, application each year. DT50 290 days (longest 1^st order un-normalised DT50 calculated by RMS from field dissipation studies). M-01 DT50 315 days, 11.9% w/w conversion from parent. Incorporation into 5cm depth of soil due to lack of cultivation.

Application data

See above

Metabolite

Method of calculation

Based on accumulated parent concentration in vines and potato adjusted for maximum observed formation of metabolite. M-02 maximum observed formation 9.6% on mass basis from field studies (16.3% molar basis); M-03 maximum observed formation 6.4% on mass basis from field studies (6.1% molar basis).

Application data

See above

Parent

Method of calculation

Field accumulation/ dissipation trials were evaluated further.

The accumulation potential of parent and M-01 at each trial site were evaluated using SFO kinetics. (M-02 and M-03 were not considered since M-02 was detected occasionally at low levels and M-03 was only detected in acidic soils).

Concentrations were converted from mg/kg to g/ha for total soil depth assuming soil density of 1.5 g/cm³. Plateau concentrations over each trial duration were reported. Potential accumulation in successive years was estimated by least squares optimisation of SFO degradation rate constants and initial soil residue in an Excel spreadsheet (using Solver tool). Predicted plateau concentrations were compared to the measured experimental data.

RMS considers that:

Overall data indicated that parent fluopicolide appeared to have reached a plateau concentration within the study duration at Phillipsburg and Senas sites. The data were considered inconclusive as to whether a plateau was reached during the trial at the Appilly site.

Modelling did not predict significant increases of parent in soil in successive years after trial duration. (Comments on the fit of this modelling reported in the Addendum).

Metabolite M-01

As above, with parent compound assumed to be 100% transformed to M-01.

RMS considers that:

Based on the measured data there was insufficient evidence of a plateau concentration being reached at Philippsburg and Appilly sites, although it did appear to be reached at Senas site.

Concentrations of M-01 were not predicted to increase significantly in soil in successive years after trial duration. However based on the modelling data, concentrations of M-01 compared to the measured data were underestimated at later time points for Philippsburg, overestimated at Senas and generally close to measured data at Appilly, with some initial under-estimation.

Route and rate of degradation in water (Annex IIA, point 7.2.1)

Hydrolytic degradation of the active substance and metabolites > 10 % ‡	Fluopicolide Stable (i.e. <10% degradation during study) at 50˚C (5 day duration) and 25 ˚C (30 day duration) at pH 4, 7 and 9
	M-01 Stable (i.e. <10% degradation during study) at 50˚C (5 day duration) and 25 ˚C (30 day duration) at pH 4, 7 and 9
	M-03 DT50 45.5 hours at pH5 and 20 ºC DT50 4.71 hours at pH6 and 20 ºC DT50 0.75 hours at pH7 and 20 ºC DT50 0.14 hours at pH8 and 20 ºC
Photolytic degradation of active substance and metabolites above 10 % ‡	Xenon lamp, wavelengths >290 nm only, 31 day duration in 12 hour light/dark cycles, equiv. midsummer sunlight at 37.45˚N. Benzoyl labelled study. DT₅₀ 64 days under study conditions (initial concentration constrained to 100%); dark control no significant degradation over study period. Predicted DT₅₀ values for the following latitudes during the summer season were calculated: 30°N 77 days, 40°N 81 days, 50°N 88 days, 35°N 231 days (spring season, Tokyo). M-01 detected up to 4.5% by study end. Pyridinyl labelled study only conducted over 10 days, no degradation seen. Sterile natural water study conducted over 16 days, no degradation seen. Aqueous photolysis is unlikely to be a significant route of degradation in natural surface waters. M-01 stable to aqueous photolysis.
Quantum yield of direct phototransformation in water at S > 290 nm	z · 3.50x10 ^–2mol · Einstein ^-1
Readily biodegradable ‡ (yes/no)	No (NOTE FOR LABELLING PURPOSES: substance failed the 10 day window criteria but mineralisation exceeded 70% within 28 days). M-01 ‘not readily biodegradable’.

Degradation in water / sediment
Fluopicolide	Distribution (Mill Stream system, max 76.2% AR in sediment at 85 DAT; Iron Hatch system, max 40.6 % AR in sediment at 182 DAT)
Water / sediment system	pH water phase	pH sed (CaCl₂)	t. ^oC	DT₅₀-DT₉₀whole sys.	St. (r²)	DisT₅₀-DisT₉₀ water	St. (r²)	DT₅₀- DT₉₀ sed	St. (r²)	Method of calculation
Mill Stream	8.4	6.5	20	1428/4570 days	0.996	8.9/29.5 days	0.944	Not calculated		SFO, mean of 2 labels
Iron Hatch	8.3	6.6	20	873/2881 days	0.998	263/873 days	0.958	Not calculated		SFO, mean of 2 labels
Geometric mean/median				1116.5

Note: separate DegT50 for water and DegT50 for sediment not calculated. Inverse modelled DT50 in total system using TOXSWA gave geomean DT₅₀ 809 days (710.1 – 921.42 days)

M-01	Distribution: Mill Stream system, 1.5% AR in water at 135 DAT (closest to 100 day SETAC duration; 5.1% AR at 365 DAT), 1.9% AR in sediment at 135 DAT (closest to 100 day SETAC duration; 3.9% AR at 365 DAT); Iron Hatch system ,3.9 % AR in water at 135 DAT (closest to 100 day SETAC duration; 18.2% AR at 365 DAT), 0.3% AR in sediment at 85 DAT (closest to 100 day SETAC duration; 2.1% AR at 365 DAT)
Water / sediment system	pH water phase	pH sed	t. ^oC	DT₅₀-DT₉₀whole sys.	St. (r²)	DT₅₀-DT₉₀ water	r²	DT₅₀- DT₉₀ sed	St. (r²)	Method of calculation
Mill Stream	8.4	6.5	20	Effectively no degradation		Not calc		Not calc		SFO degradation rate only
Iron Hatch	8.3	6.6	20	Effectively no degradation		Not calc		Not calc		SFO degradation rate only
Geometric mean/median

M-02	Distribution: Mill Stream system, 0.8% AR in water at 135 DAT, 0.8% AR in sediment at 135 DAT; Iron Hatch system, 3.3 % AR in water at 135 DAT (closest to 100 day SETAC duration; 7.4% AR at 365 DAT), 0.1% AR in sediment at 28 DAT (within 100 day SETAC duration; 0.8% AR at 365 DAT)
Water / sediment system	pH water phase	pH sed	t. ^oC	DT₅₀-DT₉₀whole sys.	St. (r²)	DT₅₀-DT₉₀ water	r²	DT₅₀- DT₉₀ sed	St. (r²)	Method of calculation
Mill Stream	8.4	6.5	20	9.1 d		Not calc		Not calc		SFO degradation rate only with TopFit
Iron Hatch	8.3	6.6	20	1517 d		Not calc		Not calc		SFO degradation rate only with TopFit
Geometric mean/median

Mineralization and non extractable residues
Water / sediment system	pH water phase	pH sed	Mineralization x % after n d. (end of the study).	Non-extractable residues in sed. max x % after n d	Non-extractable residues in sed. max x % after n d (end of the study)
Mill Stream	8.4	6.5	1.2 – 1.3% at 365 d	7.9 – 10.3% at 182 d	6.1 – 9.7% at 365 d
Iron Hatch	8.3	6.6	1.9 – 2.8% at 365 d	6.6 – 7.7% at 182 d	4.9 – 5.8% at 365 d

PEC (surface water) and PEC sediment (Annex IIIA, point 9.2.3)

Fluopicolide

Parameters used in FOCUSsw step 1, 2 and 3

Parameter	Fluopicolide
Molecular weight	383.59
Vapour pressure (Pa)	3.03 x 10^-7 at 20˚C
Solubility (mg/l)	3.02 at 20˚C
Plant uptake	0.5
Soil degradation
DT50, 20˚C & pF2	138.8 days²
Water/Sediment (20˚C)
Whole system DT50	809 days
WaterDegT50	809 days
Sediment DegT50	809 days
Adsorption
Koc	321.1
1/n	0.9028

² = Derived from field dissipation studies

Application rate

Vines

3 x 133 g a.s./ha, GS 53 – 77 N & S Europe (up to GS81 in Czech Rep), 10 - 14 day interval.

Step 1-2: crop interception set to ‘full canopy’. ‘Late vines’ chosen. Applicant used ‘Southern Europe, Mar – May’; this provides the worst case PEC values for any combination of Northern Europe or Southern Europe with March – May and June – September timings.

Step 3: two application scenarios, ‘early’ and ‘late’, but crop option chosen in Step 3 is ‘late vines’. It should be noted that this is a worst case in terms of spray drift, but it is not known what influence this has on crop interception. Minimum application window is 50 days, but in all cases has been set longer by the Applicant as detailed below.

Application window details for FOCUSsw Step 3 modelling of fluopicolide on vines:

PEC (ground water) (Annex IIIA, point 9.2.1)

Method of calculation and type of study (e.g. modelling, field leaching, lysimeter )

For FOCUS gw modelling, values used –

Model(s) used: (with version control no.(s))

PEARL3.3.3 see below for input parameters

PELMO 3.3.2 see below for input parameters.

Scenarios (list of names):

Vines:

Châteaudun, Hamburg, Kremsünster, Piacenza, Porto, Sevilla, Thiva.

Potatoes:

Châteaudun, Hamburg, Jokioinen, Kremsünster, Okehampton, Piacenza, Porto, Sevilla, Thiva.

See degradation and sorption input parameters below. Degradation parameters were calculated from field dissipation data.

Metabolites: M-01, M-02, M-03, M-05, M-10, M-11, M-12, M-13 and M-14. See input parameters below.

Application rate

Vine: 3 applications of 133 g/ha at 10 day intervals. Timing – first application set to 5 weeks after leaf emergence. Crop interception set to 60 +70+ 70%.

Potato: 4 applications of 100 g/ha at 5 day intervals, applied (i) every year, (ii) every 2 years and (iii) every 3 years. Timing – first application set to 3 weeks after emergence.

Summary of degradation and sorption parameters used in FOCUS groundwater scenarios

Compound	FOCUS scenario	DT₅₀ (days)	K_oc (L/kg)	K_om (L/kg)	Freundlich exponent (1/n)
Fluopicolide	All	138.8 ^a	321.1	186.2	0.9028
M-03	pH < 6	55.5 ^c	108.8	63.1	0.9707
M-03	pH > 6	0.09^d	108.8	63.1	0.9707
M-01	All	137.7	40.9	24	0.9158
M-02	All	2.82	5.99	3.47	0.7737
M-05 (P1x)	All	42.6	25.9	15	0.9182
M-10 (P4)	All	26.4	6.3	3.7	0.9*
M-14 (P7)	All	5.2	19.2	11.14	0.9*
M-11 and M-12	All	35.95	0	0	0.9*
M-13	All	11.8	0	0	0.9*

^a standard overall degradation half-life used in PELMO

^c in acidic soils (Hamburg, Jokioinen, Okehampton, Porto)

^d in alkaline soils (Châteaudun, Kremsmünster, Piacenza, Sevilla, Thiva)

* default 1/n

Formation fractions used for FOCUS PEARL and PELMO scenarios

Compound	FOCUS scenario	Formation fraction	k_ij (d^-1)
f (fluopicolide ® M-02/M-01)	pH < 6	0.712	0.00356
f (fluopicolide ® M-02/M-01)	pH > 6	0	0
f (fluopicolide ® M-03)	pH < 6	0.288	0.00144
f (fluopicolide ® M-03)	pH > 6	1	0.00499
f (M-03 ® M-02/M-01)	pH < 6	1	0.01249
f (M-03 ® M-02/M-01)	pH > 6	1	7.7016
f (M-02 ® M-05)	all	0.203	0.05
f (M-02 ® M-10)	all	0.095	0.0233
f (M-02 ® M-13)	all	0.062	0.0152
f (M-02 ® CO₂)*	all	0.587	0.1444
f (M-02 ® M-14)	all	0.053	0.013
f (M-05 ® M-14)	all	0.384#	0.006248^#
f (M-05 ® CO₂)	all	0.748	0.01002^#
f (M-14 ® CO₂)	all	1	0.1333
f (M-10® CO₂)	all	1	0.02622
f (M-13 ® CO₂)	all	1	0.05864

^# = worst case values used.

Fate and behaviour in air (Annex IIA, point 7.2.2, Annex III, point 9.3)

Direct photolysis in air ‡	Not studied - no data requested
Quantum yield of direct phototransformation	active substance: 3.50x10 ^–2mol · Einstein ^-1
Photochemical oxidative degradation in air ‡	Atkinson calculation using AOPWIN v.1.90. Rate constant 4.757 x 10^-12 cm³/molecule/sec. Atmospheric half life 3.373 days assuming 24 hour OH radical concentration of 0.5 x 10⁶ radicals/cm³.
Volatilisation ‡	from plant surfaces (BBA guideline): no data submitted
	from soil surfaces (BBA guideline) no data submitted
Metabolites	None

Residues requiring further assessment

Environmental occurring metabolite requiring further assessment by other disciplines (toxicology and ecotoxicology) or for which a groundwater exposure assessment is triggerred.

Soil: fluopicolide and metabolites M-01, M-02 and M-03

Surface Water: fluopicolide and soil metabolites M-01, M-02 and M-03

Sediment: fluopicolide and soil metabolites M-01, M-02 and M-03

Ground water: fluopicolide and metabolites M-01, M-02, M-03, M-05, M-10, M-11, M-12, M13 M-14 and M15

Air: fluopicolide

Monitoring data, if available (Annex IIA, point 7.4)
Soil (indicate location and type of study)	New active substance, none available
Surface water (indicate location and type of study)	New active substance, none available
Ground water (indicate location and type of study)	New active substance, none available
Air (indicate location and type of study)	New active substance, none available

Points pertinent to the classification and proposed labelling with regard to fate and behaviour data

R53 is proposed

Propamocarb-HCL

For propamocarb-HCl the LoEP included in the EFSA conslusion d.d. May 2006 is used for the assessment.

List of Endpoints Fate/behaviour

Route of degradation (aerobic) in soil (Annex IIA, point 7.1.1.1.1)

Mineralization after 100 days ‡

At 20 °C:

11.7-52.5% AR after 90d (n = 9)

At 25 °C

82.2-83.6% AR after 90d (n = 2)

Two different radiolabelled versions (aminopropyl-1-[¹⁴C] and aminopropyl-2-[¹⁴C]) of propamocarb hydrochloride were used in the fate studies. The position of radiolabelling was not observed to have an effect on any fate endpoint.

Non-extractable residues after 100 days ‡

NER maximum levels

17.8-49.0% AR after 90d at 20 °C (n=9)

11.8-12.6% AR after 90d at 25 °C (n=2)

Relevant metabolites - name and/or code, % of applied ‡ (range and maximum)

Transient unidentified metabolites reached maximum individual levels ranging from 1.0-8.7% of applied radioactivity (time of maximum occurrence = 0-90 days) (n = 22 incubations; 15 soils tested – 9 soils incubated at 20 °C, 3 soils incubated at 10 °C, 1 soil incubated at 15 °C, 1 soil incubated at 22 °C, 5 soils incubated at 25 °C)

Route of degradation in soil - Supplemental studies (Annex IIA, point 7.1.1.1.2)

Anaerobic degradation ‡

n = 2 soils (>30 days conditioning under anaerobic conditions followed by 121-365 days anaerobic incubation)

Mineralisation: CO₂ = 1.9, 3.5, and 7.7% after 365, 121, and 90 days, respectively

Non-extractable residues: 8.1, 33.5, and 40.64% after 14, 269, and 121 days, respectively

Metabolites:

Transient unidentified metabolites reached maximum individual levels of <2.0% and 6.65% after 180 and 365 days, respectively

Soil photolysis ‡

n = 2 soils

Mineralisation: CO₂ = 1.9-2.7% after 31 days (irradiated samples), CO₂ = 0.0-8.8% after 31 days (non-irradiated samples)

Non-extractable residues: 9.5-21.0% after 31 days (irradiated samples), 6.6-15.6% after 31 days (non-irradiated samples)

Metabolites:

Transient unidentified metabolites reached maximum individual levels of 1.0% and 8.7% after 14 and 30 days, respectively

Rate of degradation in soil (Annex IIA, point 7.1.1.2, Annex IIIA, point 9.1.1)

Method of calculation	Laboratory: Aerobic studies on propamocarb hydrochloride – non-linear simple first order, mono-exponential regression of parent (using Microsoft Excel tools Solver and RATEFIT). Where a short lag phase was observed the lag time data was fitted using zero-order degradation. Aerobic studies on metabolites – not applicable Anaerobic study – non-linear simple first order, mono-exponential and simple linear first order regression of parent, was used for the total system. A bi-exponential equation was used for the water phase. Soil photolysis study – non-linear simple first order, mono-exponential and simple linear first order regression, accounting for the effect of non-photolytic degradation Saturated zone degradation studies – not applicable Field studies: Non-linear simple first order regression of parent.
Laboratory studies ‡ (range or median, with n value, with r² value)	Aerobic studies (HCl: hydrochloride): Propamocarb HCl DT_50lab (20 °C, aerobic): 10.9, 11.7, 14.1, 17.8, 22.4, 23.4, 29.7, 87.7, 137 days (n = 9 soils, r² = 0.91-0.98), mean = 39.3 days Propamocarb HCl DT_50lab (25 °C, aerobic): 10.0, 13.0, 14.0, 28.0 days, (n = 3 soils) mean = 16.25 days Propamocarb HCl DT_50lab (22 °C, aerobic): 17.7 days (n = 1 soil) Metabolites: Not applicable For FOCUSgw modeling (two studies): Propamocarb HCl DT_50lab (aerobic, 1^st order kinetics): mean = 17.08 days and 10.20 days (normalised to 10kPa, 20 °C with Q10 of 2.2) If the datasets of both notifiers are considered as a whole, the geometric mean DT₅₀ value of laboratory aerobic topsoil values normalised to 20 °C and pF2 moisture content from both datasets is 13.91 days (n = 17 values). Metabolites: Not applicable
	Propamocarb HCl DT_90lab (20 °C, aerobic): 36.1-452.0 days (n = 8 soils, r² = 0.91-0.98), mean = 130.6 days Propamocarb HCl DT_90lab (25 °C, aerobic): 17.0-72.4 days (n = 3 soils), mean = 35.5 days Propamocarb HCl DT_90lab (22 °C, aerobic): 27.8 days (n = 1 soil) Metabolites: Not applicable
	(10 °C, aerobic): laboratory values Propamocarb HCl DT_50lab (10 °C, aerobic): 25.3, 47.2, 73.7 days (n = 3 soils, r² = 0.93), mean = 48.7 Propamocarb HCl DT_50lab (15 °C, aerobic): 22.0, 24.0 days (n = 2 soils), mean = 23.0 days Metabolites: Not applicable Propamocarb HCl DT_90lab (10 °C, aerobic): 84.1, 156.9, 245.0 days (n = 3 soils, r² = 0.93), mean = 162.0 Propamocarb HCl DT_90lab (15 °C, aerobic): 73.1, 79.7 days (n = 2 soils), mean = 76.4 days Metabolites: Not applicable
	Anaerobic soil: Propamocarb HCl DT_50lab (20 °C, anaerobic): 65.68-308.16 days (n = 1 soil type, 2 incubations, r² = 0.9815-9838) Propamocarb HCl DT_50lab (25 °C, anaerobic): 459.0 days (n = 1 soil, r² = 0.76) Metabolites: Not applicable [Rates are whole-system values (soil and flood water combined)] Anaerobic water phase: Propamocarb HCl DT_50lab (20 °C, anaerobic): 7.03-14.70 days (n = 1 water system type, 2 incubations, r² = 0.9797-0.9873) Metabolites: Not applicable
	Soil photolysis: Propamocarb HCl DT_50lab (irradiated samples): 35.4, 199.2 days (8 h light, 16 h dark, and 12 h light and dark photoperiods) (n = 2 soils, r² = 0.812-0.819) mean = 117.3 days Propamocarb DT_50lab (dark control samples): 103.1 days (n = 1 soil, r² = 0.86) Metabolites: Not applicable
	Aerobic subsoil degradation (n = 1 soil, 10 °C): Propamocarb HCl DT_50lab (aerobic): 73.7, 136.0, 239.0, 267.0 days (n = 4 subsoil horizons 20-90cm) mean = 178.9 days Metabolites: Not applicable
Field studies ‡ (state location, range or median with n value)	DT_50f: USA, Georgia, loamy sand (bare soil): Propamocarb HCl DT_50field: 17.6 days (n = 1, r² = 0.76) USA, Georgia, loamy sand (thatch): Propamocarb HCl DT_50field: 17.4 days (n = 1, r² = 0.78) Metabolites: Not applicable USA, California, sandy loam (bare soil): Propamocarb HCl DT_50field: 22.1 days (n = 1, r² = 0.99) USA, California, sandy loam (thatch): Propamocarb HCl DT_50field: 23.7 days (n = 1, r² = 0.92) Metabolites: Not applicable
	DT_90f: USA, Georgia, loamy sand (bare soil): Propamocarb HCl DT_90field: 58.6 days (n = 1, r² = 0.76) USA, Georgia, loamy sand (thatch): Propamocarb HCl DT_90field: 57.7 days (n = 1, r² = 0.78) Metabolites: Not applicable USA, California, sandy loam (bare soil): Propamocarb HCl DT_90field: 73.3 days (n = 1, r² = 0.99) USA, California, sandy loam (thatch): Propamocarb HCl DT_90field: 78.6 days (n = 1, r² = 0.92) Metabolites: Not applicable
Soil accumulation and plateau concentration ‡	Not applicable

Soil adsorption/desorption (Annex IIA, point 7.1.2)

K_f /K_oc ‡

K_d ‡

pH dependence ‡ (yes / no) (if yes type of dependence)

Propamocarb HCl (topsoil):

K_f: 0.671-77.20 mL/g (mean = 10.50 mL/g, 12 soils)

K_foc: 41.0-2451.0 mL/g (mean = 535.56 mL/g, 12 soils)

1/n: 0.822-0.926 (mean = 0.867, 12 soils)

K_d: 1.34-17.6 mL/g (mean = 7.77 mL/g, 4 soils)

K_oc: 59.14-1680.79 mL/g (mean = 718.81 mL/g, 4 soils)

Propamocarb HCl (subsoil horizons):

K_f: 0.72-1.04 mL/g (mean = 0.93 mL/g, 1 soil)

K_foc: 171.0-3600.0 mL/g (mean = 1190.0 mL/g, 1 soil)

1/n: 0.86-0.91 (mean = 0.872, 1 soil)

[K_foc = K_f normalized to organic carbon content, K_oc = K_d normalized to organic carbon content]

Metabolites: not applicable

No obvious pH dependence for Propamocarb. However, there is a possibility that adsorption to soil may depend on the clay content of the soil.

Mobility in soil (Annex IIA, point 7.1.3, Annex IIIA, point 9.1.2)

Column leaching ‡

Guideline: BBA Part IV, Section 4-2 (1986)

Precipitation: 200 mm

Time period: 5 days

Leachate: 0.043-0.260% total residues in leachate, 37.0-92.8% radioactivity retained in top 5 cm, 0.5-41.62% radioactivity retained in 5-10 cm column segment, 0.5-13.1% radioactivity retained in 10-15 cm column segment, <0.1-0.2% radioactivity retained in 15-20 cm column segment, <0.1% radioactivity retained in the remaining segments 20-25 cm and 25-30 cm

Aged residues leaching ‡

Guideline: SETAC (1995), Part 1, Section 6

Aged for: 12 days (Midwest 3), 23 days (Speyer 2.3)

Time period: 2 days

Precipitation: 200 mm

Leachate: 0.67-0.90% radioactivity in leachate, 27.88-44.49% radioactivity retained in top 6 cm, 6.21-14.86% radioactivity retained in 6-12 cm column segment, 1.60-10.90% radioactivity retained in 12-18 cm column segment, 0.28-3.90% radioactivity retained in 18-24 cm column segment, 0.07-1.06% radioactivity retained in 24-30 cm column segment

Lysimeter/ field leaching studie ‡

Not required

Route and rate of degradation in water (Annex IIA, point 7.2.1)

Hydrolysis of active substance and relevant metabolites (DT₅₀) ‡ (state pH and temperature)	pH 4 and pH 5 (HCl: hydrochloride) Propamocarb HCl DT₅₀ (pH 4 & 5, 50 °C): stable (DT₅₀ >365 days) Propamocarb HCl DT₅₀ (pH 4 & 5, 25 °C): stable (DT₅₀ >365 days) Metabolites: not applicable
	pH 7 Propamocarb HCl DT₅₀ (50 °C): stable (DT₅₀ >365 days) Propamocarb HCl DT₅₀ (25 °C): stable (DT₅₀ >365 days) Metabolites: not applicable
	pH 9 Propamocarb HCl DT₅₀ (50 °C): stable (DT₅₀ >365 days) Propamocarb HCl DT₅₀ (25 °C): stable (DT₅₀ >365 days) Metabolites: not applicable
Photolytic degradation of active substance and relevant metabolites ‡	Propamocarb HCl: (pH 4-5, 24 °C) stable [Irradiation with artificial light, stated to be equivalent to 4´ light intensity seen in summer at Les Borges, Switzerland.] UV-VIS study indicates that wavelength of maximum absorption is <250 nm. Irradiation at wavelengths ³290 nm are not expected to induce any photochemical transformation. Metabolites: not applicable
Readily biodegradable (yes/no)	[Mean cumulative CO2 production data obtained from Propamocarb HCl test mixtures are ambivalent. Results from a study indicate highly variable CO2 evolution from test replicates. However, Propamocarb HCl route and rate of degradation has been extensively investigated in soil metabolism and water/sediment studies.]
Degradation in water/sediment DT₅₀ water ‡ DT₉₀ water ‡ DT₅₀ whole system ‡ DT₉₀ whole system ‡	[Two aerobic studies provided and one anaerobic study for Propamocarb HCl] Water phase: Propamocarb HCl (aerobic) DT₅₀ = 11.6-12.0 days, DT₉₀ = 38.4-39.9 days (1^st order, n = 2, r² = 0.894-0.967) Propamocarb HCl (aerobic) DT₅₀ = 10.0-15.0 days, DT₉₀ = 34.0-49.0 days (non-linear 1^st order using KIM B1.0 model, n = 2) Metabolites: not applicable Propamocarb HCl (anaerobic) DT₅₀ = 12.1 days, DT₉₀ = 40.1 days (linear 1^st order regression, n = 1) Metabolites: not applicable Whole system: Propamocarb HCl (aerobic) DT₅₀ = 15.5-15.9 days, DT₉₀ = 51.5-52.7 days (1^st order, n = 2, r² = 0.905-0.913) Propamocarb HCl (aerobic) DT₅₀ = 16.0-21.0 days, DT₉₀ = 53.0-69.0 days (non-linear 1^st order using KIM B1.0, n = 2) Metabolites: not applicable Propamocarb HCl (anaerobic) DT₅₀ = 100.0 days, DT₉₀ = 332.3 days (linear 1^st order regression, n = 1) Metabolites: not applicable
Mineralization	CO₂ maximum (aerobic) = 67.5-94.7% (at 104-105 days, study end, n = 4) CO₂ maximum (anaerobic) = 69.0 % (at 370 days, study end, n = 1)
Non-extractable residues	Non-extractable maximum residues (aerobic) = 10.3-16.0% (at 42-63 days, n = 4) Non-extractable maximum residues (anaerobic) = 20.1% (at 110 days, n = 1)
Distribution in water / sediment systems (active substance) ‡	Water phase: Propamocarb HCl (aerobic) = 87.0-102.3% (day 0), 82.7-86.9% (day 1) and not detected by day 104/105 (n = 4 systems) Propamocarb HCl (anaerobic) = 100.9% (day 0), 53.3% (day 13), 0.3% (day 370) (n = 1 system) Sediment phase: Propamocarb HCl (aerobic) = 12.4-21.5% (day 1), 15.8-36.9% (7-28 days), 0.0-5.6% (104/105 days) (n = 4 systems) Maximum of 36.9% applied radioactivity in sediment after 14 days. DT₅₀ in sediment (aerobic) 23-26 days (1^st order, n = 2) Propamocarb HCl (anaerobic) = 2.0% (day 0), 80.1% (day 54), 14.0% (day 370) (n = 1 system) Maximum of 80.1% applied radioactivity in sediment after 54 days. DT₅₀ in sediment (anaerobic) 93 days (1^st order, n = 1) [Dosing method – application to water, no mixing]
Distribution in water / sediment systems (metabolites) ‡	Transient unidentified metabolites reached maximum individual levels in aerobic water and sediment phases combined of 1.7-5.6% of applied radioactivity (time of maximum occurrence = 7-28 days) (n = 4 systems, incubated at 20 °C) Transient unidentified metabolites reached maximum individual levels in anaerobic water and sediment phases of 3.9% and 0.9%, respectively (time of maximum occurrence = 13 days) (n = 1 system, incubated at 25 °C)

Fate and behaviour in air (Annex IIA, point 7.2.2, Annex III, point 9.3)

Direct photolysis in air ‡	Not determined – no data requested
Quantum yield of direct phototransformation	Not determined in air
Photochemical oxidative degradation in air ‡	DT₅₀ = 4.03 and 13.4 hours (Atkinson method)
Volatilization ‡	From plant surfaces: Propamocarb hydrochloride was found to volatilise from plant surfaces (French beans) <10.0%, this value is less than the BBA trigger value of 20.0% in volatilisation studies conducted over a 24 hour period.
	from soil: volatilisation loss of Propamocarb hydrochloride is estimated to be <0.0001% of the applied amount within 24 hours after treatment (Dow method) and was found to evaporate <15.0% in volatilisation studies conducted over a 24 hour period, which is less than the BBA trigger value of 20.0%.

Definition of the Residue (Annex IIA, point 7.3)

Relevant to the environment

Soil:

Propamocarb and its salts, expressed as propamocarb

Water (surface and ground water):

Propamocarb and its salts, expressed as propamocarb

Air:

Propamocarb and its salts, expressed as propamocarb

Monitoring data, if available (Annex IIA, point 7.4)

Soil (indicate location and type of study)	Relevant European data not available
Surface water (indicate location and type of study)	Relevant European data not available
Ground water (indicate location and type of study)	Relevant European data not available
Air (indicate location and type of study)	Relevant European data not available

Classification and proposed labelling (Annex IIA, point 10)

with regard to fate and behaviour data

Candidate for

R53 May cause long-term adverse effect in the aquatic environment

Appendix A: Metabolite names, codes and other relevant information of the pesticide Infinito with a.s. fluopicolide and propamocarb-HCl.

The compounds shown below were found in one or more studies involving the metabolism and/or environmental fate of fluopicolide and propamocarb. The parent compound structure of fluopicolide (AE C638206) is shown first in this list and followed by degradate or related compounds. Than the parent compound structure of fluopicolide (AE C638206) is shown.

Compound name	Code number(s)	IUPAC name	Structural formula	Structure	Molecular Weight [g/mol]	Observed in study (% of occurrence/ formation)
fluopicolide	(AE C638206)	2,6-dichloro-N-[3-chloro-5-(trifluoromethyl)-2-pyridylmethyl]benzamide	C₁₄H₈Cl₃F₃N₂O		383.59	Bv Soil (lab degradation): x % Water: xx % Sediment (mesocosm): Air
M01	(AE C653711)	2,6-dichlorobenzamide (BAM)				25% in soil
M02	(AE C657188)	3-chloro-5-(trifluoromethyl)pyridine-2-carboxylic acid				2x 5% in soil
M03	(AE 0608000)	2,6-dichloro-N-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl](hydroxy)methyl}benzamide				10.6% in soil
M05	(AE 1344122)	3-(methylsulfinyl)-5-(trifluoromethyl)pyridine-2-carboxylic acid				>0.1 lysimeter
M10	(AE 1344123)	3-sulfo-5-(trifluoromethyl)pyridine-2-carboxylic acid				>0.1 lysimeter
M11		6-hydroxy-3-sulfo-5-(trifluoromethyl)pyridine-2-carboxylic acid				>0.1 lysimeter
M12		4-hydroxy-3-sulfo-5-(trifluoromethyl)pyridine-2-carboxylic acid				>0.1 lysimeter
M13		3-chloro-4-hydroxy-5-(trifluoromethyl)pyridine-2-carboxylic acid				>0.1 lysimeter
Propamocarb HCl		Propyl 3-(dimethylamino) propylcarbamate hydrochloride	(C9H21ClN2O2)		224.7	parent

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[4] method. Currently this method equals the method described in the Technical Guidance Document (TGD). Additional guidance is presented in RIVM[5]-report 601782001/2007[6].

For the current application this means the following:

fluopicolide

The following normalised laboratory DT₅₀ values are available for the active substance fluopicolide: 277, 276, 300,194, 266 and 333 days (geomean 271 days).

Due to the exceeding of the threshold value of 60 days for the mean DT₅₀ (lab) for fluopicolide, it must be demonstrated by means of field dissipation studies that the field DT₅₀ is < 90 days. The following relevant best fit non-normalised field data are provided: 99, 132, 172, and 104 days (geomean 124 days). Data from Spain and Southern France are not used for the Dutch assessment.

For the metabolite M01 the following normalised laboratory DT₅₀-values are available: 1848, and 808 days.

Due to the exceeding of the threshold value of 60 days for the mean DT₅₀ (lab) for M-01 (BAM), it must be demonstrated by means of field dissipation studies that the field DT₅₀ is < 90 days. The following relevant non-normalised best-fit field data are provided:120, 315, and 186 days (geomean 191.6 days)

From the results it is shown that the mean field DT50 is > 90 days.

Based on the above, the proposed applications of the pesticide infinito do not meet the standards for persistence as laid down in the RGB. Because the field DT₅₀ is > 90 days, it has to be demonstrated that application of the pesticide does not lead to accumulation of the a.s. fluopicolide and metabolite M01 (BAM) to the extent that it will have an unacceptable effect on non-target-organisms. In order to prevent this, the sum of the concentrations in which the a.s. fluopicolide and the metabolite M01 are present 2 years after the last application after 10 years of annual application in the upper 20 cm of the soil where the pesticide has been applied (Gp,10) (see Table M.4), should not exceed the MPC-INS value for soil organisms.

For the metabolite M02 the following normalised laboratory DT₅₀-values are available: 3, 2.5 and 3 days (geomean 2.8 days).

For the metabolite M03 the following normalised laboratory DT₅₀-values are available: 1.7, 4.7, 0.1 and 0.09 days (geomean 0.5 days).

For the metabolite M05 the following normalised laboratory DT₅₀-values are available: 41, 100, 22, 20.7, 90.7 and 35.2 days (geomean 42.6 days).

For the metabolite M10 the following normalised laboratory DT₅₀-values are available: 194, 24, 16, 3, 236 and 6.4 days (geomean 26.4 days).

For the metabolite M14 the following normalised laboratory DT₅₀-values are available: 6.3, 3.3, 3.8, 5.3 and 9.1 days (geomean 5.2 days).

For the metabolite M11/M12 the following normalised laboratory DT₅₀-values are available: 27.3, 66.2, and 25.8 days (geomean 36 days).

For the metabolite M13 the following normalised laboratory DT₅₀-values are available: 7.3, 33.1, and 6.9 days (geomean 11.8 days).

Based on the above, the standards of persistence as laid down in the RGB are met for metabolites M02, M03, M05, M10, M14, M11/M12 and M13.

Propamocarb-HCl

The following laboratory DT₅₀ values at 20°C are available for the active substance propamocarb HCl: 10.9, 11.7, 14.1, 17.8, 22.4, 23.4, 29.7, 87.7, 137 days (mean 39.3 days, geomean = 26.3 days). The following laboratory DT₅₀ values at 25°C are available for the active substance propamocarb HCl: 10.0, 13.0, 14.0 and 28 days (mean = 16.25 days). The following laboratory DT₅₀ value at 22°C is available for the active substance propamocarb HCl: 17.7 days. The overall geomean of all the above data normalised to 20 °C and pF2 (n=17, data both notifiers) is 13.9 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.

MPCsoil

In RIVM report 12639A01 the MPC (maximum permissable concentration, Dutch: MTR) for soil is derived for a.s. fluopicolide. In RIVM report 12645A01 the MPC (maximum permissable concentration, Dutch: MTR) for soil is derived for metabolite M01, BAM.

fluopicolide

Data sources

The derivation of the MPC for fluopicolide is based on the data available in the EU-dossier. Data from the Draft Assessment Report were re-assessed for their reliability in view of the specific use for MPC-derivation. In addition, an on-line literature search was performed via SCOPUS, available via http://www.scopus.com/. For information on coverage, see http://info.scopus.com/detail/what/

The following search was performed:

((TITLE-ABS-KEY(fluopicolide) OR CASREGNUMBER(239110-15-7)) AND ((TITLE-ABS-KEY(plant* OR microorganism* OR springtail* OR earthworm* OR Eisenia)) OR (TITLE-ABS-KEY(soil* OR earth)) OR (TITLE(terrestrial)) OR (SRCTITLE(terrestrial)))) AND ((TITLE-ABS-KEY(bioassay* OR toxic* OR ecotoxic* OR mortalit* OR sensitiv* OR phytotox* OR reproduct* OR lethal* OR growth OR teratogen* OR ec50* OR ec20* OR ec10* OR lc50* OR lc20* OR lc10* OR noec* OR loec* OR matc OR tlm OR chv OR ecx OR bioassay*)) OR (TITLE(expos* OR respons* OR effect* OR impact OR toxic* OR ecotoxic* OR mortalit* OR sensitiv* OR assess*)))

This search did not result in any references from which an endpoint could be derived. Further, an RIVM report (no. 10904a00) containing information regarding to route and rate of degradation in soil and adsorption, desorption and mobility in soil was available for fluopicolide. However, in this report was stated that the original study reports were not available and that these reports are essential for the assessment of the studies and (if neccessary) recalculation of results. Therefore, only information from the DAR is used for determination of DT₅₀ and K_oc values for fluopicolide.

Data for human toxicology and secondary poisoning:

If no suitable data are available, according to the INS-method no MPC is derived for these two routes, without further consequences for the final MPC.

Bioconcentration and biomagnification

Since the geometric mean of the log K_ow values is > 3 (3.5), the trigger for bioconcentration and biomagnification is exceeded and a risk for bioconcentration and biomagnification could occur. The MPC_{sp, soil} for secondary poisoning is derived below.

Human toxicological threshold limits and carcinogenicity

Fluopicolide is proposed to be assigned no R-phrases for effects on human health.

For the plant protection product 'EXP 11074B' (fluopicolide 44.4 g/kg + fosetyl-aluminium 666.7 g/kg), R36 and the hazard symbol Xi are proposed. For the plant protection product 'EXP 11120A' (fluopicolide 62.5 g/L + propamocarb hydrochloride 625 g/L), R43 and the hazard symbol Xi are proposed.

For ecotoxicological effects, both the active substance and the two plant protection products are proposed to be assigned R50/53 and the hazard symbol N.

The ADI is 0.08 mg/kg bw/d, based on a 78-week dietary study in mice (NOAEL 7.9 mg/kg bw/d, assessment factor 100). The MPC_human,
soil is derived as describerd below.

Ecotoxicological effect data

Laboratory data

The available chronic ecotoxicity data for soil organisms and/or processes are summarised in Table M.1.

Table M.1 Ecotoxicity data for soil organisms (lowest value in bold)

Taxonomic group and processes	L(E)C₅₀ standard soil 10% OM [mg/kg_dwt]	NOEC standard soil 10% OM [mg/kg_dwt]	Remark
Bacteria
Soil microflora		≥ 4.49	Nitrogen transformation
Soil microflora		≥ 30.7	Carbon transformation

Fungi
Mucor circinelloides		≥ 300
Phytophora nicotianae		3
Cladorrhinum foesundissimum		≥ 300
Penicilium janthinellum		≥ 300
Suillus granulatus		≥ 300

Annelida
Eisenia foetida	> 1000	125

Insecta
Folsomia candida		62.5

Field data

No field data were available for fluopicolide.

Derivation of the MPCsoil

MPCeco, soil – ecotoxicity data

According to the INS-Guidance (Section 2.2.2.8), part of the endpoints presented in Table M.1 cannot be used for the derivation of the MPC_{eco, soil} because in some the studies the test concentration was not high enough to determine the NOEC or L(E)C₅₀.

NOECs are available for three species from two trophic levels. The MPC_{eco, soil} is derived by using an assessment factor of 50 to the lowest NOEC (3 mg/kg_dwt derived in a 6-d study with the fungi Phytophora nicotianae), resulting in an MPC_{eco, soil} of 0.06 mg/kg_dwt

MPCsp, soil – secondary poisoning

Since the log K_ow is ≥ 3, the MPC_soil via secondary poisoning is derived. The MPC_oral per species is calculated applying the appropriate assessment factor (see Table M.2). The lowest value is used for MPC derivation according to Section 3.3.5 of the INS-Guidance.

Table M.2 Toxicity data for birds and mammals

	Duration	NOAEC diet [mg/kg_diet]	AF	MPC_{oral, mammal} MPC_{oral, bird} [mg/kg diet]
Mammals
Mouse	78 weeks	50	30	1.67
Rabbit	22 days	66.6	300	0.2
Rat	2 generation	500	30	16.7
Rat	2 generation	600	30	20
Rat	13 weeks	200	90	2.22

Birds
Bobwhite quail	5 days	3160	3000	1.05
Bobwhite quail	21 weeks	1000	30	33.3
Mallard duck	5 days	1780	3000	0.59
Mallard duck	21 weeks	≥ 1000	30	33.3

Because for rats and birds more than one study is available, the most appropriate MPC_oral for these organisms should be selected first. According to the INS-Guidance (Section 3.1.4.2, point 2, last lines), it is recommended in this case “to use the most sensitive endpoint divided by the appropriate assessment factor (i.e. the factor implied by the study with the longest test duration)”.

Taking the lowest from the MPC_oral-values for rat, mouse, rabbit and bird, the MPC_oral,min is set to 1.67 mg/kg diet.

· The MPC_{oral, min} is 1.67 mg/kg diet

· A BCF value for soil organisms is not available. Using the log K_ow of 3.5, the calculated BCF is 39 kg/kg ww (Eq. 8 of the INS-Guidance; RHO_earthworm = 1)

· Using the K_oc of 318 and the Henry-coëfficient of 4.15 x 10^-5 Pa.m³/mol, the K_soil-water is calculated as 10 m³/m³ (Eq. 57, 59 and 60 of the INS-Guidance).

· Combining this input and using the default parameters as given in the INS-Guidance, the MPC_{sp, soil} is 0.30 mg/kg dwt, for standard soil with 10% OM.

MPChuman, soil – human exposure

The MPC_human,
soil is calculated according to Section 3.3.6 of the INS-Guidance, using the ADI of 0.08 mg/kg bw/d as input. Other input parameters needed for the (intermediate) calculations are the K_ow (10^3.5 = 2971) and K_oc (318) and Henry’s law constant and water solubility as given in Table 2. Using the defaults as given in Table 31 of the INS-Guidance, the following results are obtained.:

MPC_{human,soil leaf} 4.988 x 10^-8 kg/kg_{wwt soil}

MPC_{human,soil root} 1.812 x 10^-7 kg/kg_{wwt soil}

MPC_{human,soil milk} 6.278 x 10^-5 kg/kg_{wwt soil}

MPC_{human,soil meat} 3.700 x 10^-5 kg/kg_{wwt soil}

The most critical MPC_{human, soil} for exposure via leaf crops (4.988 x 10^-8 kg/kg_{wwt soil}) is equivalent to 0.17 mg/kg_dwt for standard soil at 10% OM.

Conclusion

The following MPCs are derived for the soil compartment for standard soil with 10% OM:

MPC_{eco, soil} = 0.06 mg/kg dwt

MPC_{sp, soil} = 0.30 mg/kg dwt

MPC_{human, soil} = 0.17 mg/kg dwt

The lowest of these values is selected as the final MPC_soil. The MPC_soil of fluopicolide is

0.06 mg/kg dwt soil, based on standard soil with 10% OM.

Fluopicolide metabolite M01

Data sources

The derivation of the MPC for fluopicolide metabolite M-01 is based on the data available in the EU-dossier. Data from the Draft Assessment Report were re-assessed for their reliability in view of the specific use for MPC-derivation. In addition, an on-line literature search was performed via SCOPUS, available via http://www.scopus.com/. For information on coverage, see http://info.scopus.com/detail/what/

The following search was performed:

((TITLE-ABS-KEY(fluopicolide metabolite) OR CASREGNUMBER(2008-58-4)) AND ((TITLE-ABS-KEY(plant* OR microorganism* OR springtail* OR earthworm* OR eisenia)) OR (TITLE-ABS-KEY(soil* OR earth)) OR (TITLE(terrestrial)) OR (SRCTITLE(terrestrial)))) AND ((TITLE-ABS-KEY(bioassay* OR toxic* OR ecotoxic* OR mortalit* OR sensitiv* OR phytotox* OR reproduct* OR lethal* OR growth OR teratogen* OR ec50* OR ec20* OR ec10* OR lc50* OR lc20* OR lc10* OR noec* OR loec* OR matc OR tlm OR chv OR ecx OR bioassay*)) OR (TITLE(expos* OR respons* OR effect* OR impact OR toxic* OR ecotoxic* OR mortalit* OR sensitiv* OR assess*)))

This search did not result in any references from which an endpoint could be derived.

Data for human toxicology and secondary poisoning:

If no suitable data are available, according to the INS-method no MPC is derived for these two routes, without further consequences for the final MPC.

Bioconcentration and biomagnification

Since the log K_ow is < 3, the trigger for bioconcentration and biomagnification is not exceeded. Therefore, the MPC_{sp, soil} for secondary poisoning is not derived.

Human toxicological threshold limits and carcinogenicity

Based on an oral LD₅₀ in rat of 500 mg/kg classifiaction with R 22, Xn was proposed.

The parent compount fluopicolide is proposed to be assigned no R-phrases for effects on human health. For the plant protection product 'EXP 11074B' (fluopicolide 44.4 g/kg + fosetyl-aluminium 666.7 g/kg), R36 and the hazard symbol Xi are proposed. For the plant protection product 'EXP 11120A' (fluopicolide 62.5 g/L + propamocarb hydrochloride 625 g/L), R43 and the hazard symbol Xi are proposed.

For ecotoxicological effects, both the active substance and the two plant protection products are proposed to be assigned R50/53 and the hazard symbol N.

The ADI of fluopicolide metabolite M-01 is 0.05 mg/kg bw/d, based on the long term (two-year) rat and dog studies (NOAEL 5 mg/kg bw/d, assessment factor 100). The MPC_{human, soil} is derived in Section 1.5.3.

Ecotoxicological effect data

Laboratory data

The available chronic ecotoxicity data for soil organisms and/or processes are summarised in Table 4. The lowest L(E)C₅₀ and NOEC value are presented in bold.

Table M.3 Ecotoxicity data for soil organisms

Taxonomic group and processes	L(E)C₅₀ standard soil 10% OM [mg/kg_dw]	NOEC standard soil 10% OM [mg/kg_dw]	Remark
Bacteria
Soil microflora		≥ 9.2	Nitrogen transformation
Soil microflora		≥ 9.2

Fungi
Mucor circinelloides		≥ 300
Phytophora nicotianae		≥ 300
Cladorrhinum foesundissimum		≥ 300
Penicilium janthinellum		≥ 300
Suillus granulatus		≥ 300

Annelida
Eisenia foetida	750	250

Insecta
Folsomia candida		25

Field data

No field data were available for fluopicolide metabolite M-01.

Derivation of the MPCsoil

MPCeco, soil – ecotoxicity data

According to the INS-Guidance (Section 2.2.2.8), part of the endpoints presented in Table M.3 cannot be used for the derivation of the MPC_{eco, soil} because in some the studies the test concentration was not high enough to determine the NOEC or L(E)C₅₀.

NOECs are available for two species from two trophic levels. NOECs are available for three species from two trophic levels. The MPC_{eco, soil} is derived by using an assessment factor of 50 to the lowest NOEC, resulting in an MPC_eco,
soil of 0.5 mg/kg_dwt.

MPChuman, soil – human exposure

The MPC_human,
soil is calculated according to Section 3.3.6 of the INS-Guidance, using the ADI of 0.05 mg/kg bw/d as input. Other input parameters needed for the (intermediate) calculations are the K_ow (10^0.77 = 5.89) and K_oc (worst-case, 31 L/kg) and Henry’s law constant and water solubility as given in Table 2. Using the defaults as given in Table 31 of the INS-Guidance, the following results are obtained:

MPC_{human,soil leaf} 1.161 x 10^-8 kg/kg_{wwt soil}

MPC_{human,soil root} 5.983 x 10^-7 kg/kg_{wwt soil}

MPC_{human,soil milk} 4.624 x 10^-5 kg/kg_{wwt soil}

MPC_{human,soil meat} 8.618 x 10^-4 kg/kg_{wwt soil}

The most critical MPC_{human, soil} for exposure via leaf crops (1.161 x 10^-8 kg/kg_{wwt soil}) is equivalent to 0.039 mg/kg_dwt for standard soil at 10% OM.

Conclusion

The following MPCs are derived for the soil compartment for standard soil with 10% OM:

MPC_{eco, soil} = 0.5 mg/kg dwt

MPC_{human, soil} = 0.039 mg/kg dwt

The lowest of these values is selected as the final MPC_soil. The MPC_soil of fluopicolide metabolite M-01 is 0.039 mg/kg dw soil, based on standard soil with 10% OM.

PECsoil

The concentration of the [a.s. (and metabolites)] 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 fluopicolide:

Maximum relevant non-normalised best-fit field DT₅₀ for degradation in soil: 172 days

Molecular mass: 383.59 g/mol

Metabolite M01 (BAM):

Maximum non-normalised best-fit field DT₅₀ for degradation in soil (20°C): 315 days

Molecular mass: 190.03 g/mol

Correction factor: 11.9% (maximum observed percentage in field) * 0.5 (relative molar ratio = M metabolite/M parent) = 0.06

Metabolite M03:

Maximum non-normalised lab DT₅₀ for degradation in soil (20°C): 5 days

Molecular mass: 399.6 g/mol

Correction factor: 10.6%(maximum observed percentage) * 1.04 (relative molar ratio = M metabolite/M parent) = 0.11

Active substance propamocarb-HCl:

Maximum lab/field DT₅₀ for degradation in soil: 137 days

Molecular mass: 224.7 g/mol (propamocarb-HCl); 188.3 g/mol (propamocarb)

The Gp,10 of metabolite a.s. fluopicolide and M01 (BAM) is derived based on a R% of 21.8% for fluopicolide and 5.18% for M01.

This R% is the result of a PEARL 3.3.3 calculation of an application in maize of 1 kg/ha on May 25^th with the Dutch standard scenario based on:

Active substance fluopicolide:

Geometric mean normalised field DT₅₀ for degradation in soil (20°C): 138.8 days.

Arithmetic mean K_om (pH-independent): 186.2 L/kg

Arithmetic mean 1/n: 0.903

Saturated vapour pressure: 3.03 x 10^-7 Pa (20 ºC)

Solubility in water: 2.8 mg/L (20 ºC)

Molecular mass: 383.59 g/mol

Metabolite M01 (BAM) :

Geometric mean normalised field DT₅₀ for degradation in soil (20°C): 137.7 days

Arithmetic mean K_om (pH-independent): 23.7 L/kg

Arithmetic mean 1/n: 0.9158

Maximum fraction of occurence: 1.0

Saturated vapour pressure: 2.0 x 10^-5 Pa (25˚C)

Solubility in water: 1830 mg/L (20 ºC)

Molecular mass: 190 g/mol

See Table M.4 for other input values and results.

Table M.4 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]

PECsoil

21 days

[mg a.s./kg]

PECsoil

20 cm (G_p,10)

[mg a.s./kg]

Potatoes non-professional use

Fluopicolide

M-01

M-03

Propamocarb-HCl

0.25

0.1

0.095

0.945

0.5

0.243

0.063

0.01

2.391

0.233

0.061

0.003

2.269

0.018

0.0001

* fraction on soil is detemined as 1 – interception value; interception values derived from Table 1.6 in “generic guidance for FOCUS groundwater scenarios”. based on interception percentage before flowering (BBCH 20-39 which is in the middle of the potential use period)

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

Risk assessment

Since the Gp,10 is lower than the MPCsoil of 0.06 mg/kg dw soil, 0.028 mg/kg dw soil corrected for 4.7% OM, for a.s. fluopicolide, it is concluded that the standards for persistence as laid down in the RGB are met.

Since the Gp,10 is lower than the MPCsoil of 0.039 mg/kg dw soil for metabolite BAM, it is concluded that the standards for persistence as laid down in the RGB are met.

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 0.095 kg/ha for fluopicolide and 0.945 kg/ha for propamocarb-HCl, the crop [potatoes] and an interception value appropriate to the crop of [0.5]. As the use is for non-professional only, the actual dose is considered to be 1/10 of the dose rate derived in the GAP table, based on smaller areas treated. First date of yearly application is May 25^th. For metabolites all available data concerning substance properties are regarded. Metabolites M-01, M02 and M-03 occurred in aerobic soil degradation studies and should be 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 in the aerobic soil degradation studies. Metabolite M02 has a very low DT₅₀ combined with a small Kom (both values below 10) and metabolite M03 shows a tendency to pH dependent degradation. Both metabolites should therefore be subject to GeoPEARL calculation, the second step in the leaching assessment. Nevertheless as both metabolites can be considered toxicological non-relevant a GeoPEARL calculation was not performed.

In the dossier numerous lysimeter metabolites are identified which showed leaching from the lysimeter above 0.1 µg/L. These metabolites (M-05, M-10, M-11, M-12, and M-13) are not included in the calculation. From the final assessment report (EFSA 2009) it is concluded these metabolites can be considered non-relevant. For metabolite M-15 the groundwater assessment could not be finalised because data on human toxicity are missing. In this case, as it is non-professional use only, this metabolite is not further considered.

The following input data are used for the calculation:

PEARL:

Active substance fluopicolide:

Geometric mean normalised field DT₅₀ for degradation in soil: 138.8 days (in line with EU review)

Arithmetic mean K_om (pH-independent): 186.2 L/kg

Arithmetic mean 1/n: 0.903

Saturated vapour pressure: 3.03 x 10^-7 Pa (20ºC)

Solubility in water: 3.02 mg/L (20ºC)

Molecular mass: .383.6 g/mol

Metabolite M01:

Geometric mean normalised field DT₅₀ for degradation in soil (20°C): 137.7 days ( in line with EU review)

Arithmetic mean K_om (pH-independent): 23.7 L/kg

Arithmetic mean 1/n: 0.9158

Arithmetic mean formation fraction: 0.5 from M03 (cf DAR calculation)

Maximum fraction of occurence: 0.25

Saturated vapour pressure: 2.0 x 10^-5 Pa (25˚C)

Solubility in water: 1830 mg/L (20 ºC)

Molecular mass: 190 g/mol

Metabolite M02:

Geometric mean DT₅₀ for degradation in soil (20°C): 2.8 days

Arithmetic mean K_om (pH-independent): 3.48 L/kg

Arithmetic mean 1/n: 0.774

Arithmetic mean formation fraction: 0.5 from M03 (cf DAR calculation) used for calculation

Maximum fraction of occurence: 0.073

Saturated vapour pressure: parent value

Solubility in water: parent value

Molecular mass: 225.6 g/mol

Metabolite M03:

Geometric mean DT₅₀ for degradation in soil (20°C): 0.09 days (value for soils with pH > 6

Arithmetic mean K_om (pH-independent): 63.23 L/kg

Arithmetic mean 1/n: 0.971

Arithmetic mean formation fraction: 1 from parent (cf DAR calculation)

Maximum fraction of occurence: 0.106

Saturated vapour pressure: parent value

Solubility in water: parent value

Molecular mass: 399.58 g/mol

Propamocarb-HCl:

Geometric mean normalise field DT₅₀ for degradation in soil: 12.4 days

Arithmetic mean K_om (pH-independent): 310.6 L/kg

Arithmetic mean 1/n: 0.867

Saturated vapour pressure: 1.66 x 10^-3 Pa (25ºC)

Solubility in water: no value available

Molecular mass: 224.7 g/mol

Other parameters: standard settings of PEARL 3.3.3

The following concentrations are predicted for the a.s. fluopicolide and the metabolites M01 (BAM), M02 and M03 and the active substance propamocarb-HCl following the realistic worst case GAP, see Table M.5.

Table M.5 Leaching of a.s. fluopicolide and metabolites M01, M02 and M03, and a.s. propamocarb-HCl as predicted by PEARL 3.3.3

Use

Substance

Rate substance [kg/ha]¹

Frequency

Interval [days]

Fraction

Intercepted *

PEC groundwater [mg/L]

spring

Potatoes (non-professional use)

Fluopicolide

M01

M02

M03

Propamocarb-HCl

0.0095

0.0945

0.5

0.0049

0.334

0.0001

0.0002

<0.001

* interception values derived from Table 1.6 in “generic guidance for FOCUS groundwater scenarios”. Application prescribed from BBCH 15-89, the median of this period is used for calculation.

¹ for non-prossional use it is assumed only 10% of the area is exposed

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. fluopicolide and its metabolites M02 and M03, and the a.s. propamocarb-HCl 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.

The expected leaching for the metabolite M01 of fluopicolide (BAM) equal to or larger than 0.1 µg/L. Therefore, further study into the leaching behaviour is necessary.

As from the final conclusion on the a.s. fluopicolide it can be read that all metabolites can be considered non-relevant (EFSA Scientific Report (2009) 299) and the application is for non-professional use only, the metabolites do not need to meet the standards for leaching as laid down in the RGB.

Monitoring data

There are no data available regarding the presence of the substance fluopicolide or prpamocarb-HCl in groundwater.

Regarding the presence of metabolite M01 of fluopicolide monitoring data are available.

BAM was observed in the groundwater [reference: RIVM report 607310001/2007 in Dutch]. In Table M.6 observed concentrations in groundwater are presented.

Table M.6 Monitoring data in groundwater

Location/year	Detection limit [mg/L]	a/n^*	Filter depth	90^th percentile conc. [mg/L]	Maximum conc. [mg/L]
Location	0.05	45/675	< 7 m-mv and >7 m-mv	<0.02	7.69

^*number of observations above detection limit (a)/total number observations (n).

Monitoring results indicate that the substance BAM was detected on several occasions. After evaluation of the data, the 90^th percentile concentrations did not exceed the limit of 0.1 mg/L. Quite a number of measurements could be attributed to the non-agricultural use of dichlobenil which is transformed in BAM as well. The monitoring data tend to confirm the predicted concentrations. However, BAM has been declared non relevant (EFSA Scientific Report (2009) 299) and therefore BAM meets the standards laid down in the RGB for the proposed application.

Conclusions

The proposed application of the product complies 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 substances fluopicolide and Propamocarb-HCl 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 non-professional use a drift rate of 0.5% is used.

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

TOXSWA:

Active substance fluopicolide:

Geometric mean DT₅₀ for degradation in water at 20°C: 1116.5 days

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

Arithmetic mean K_om for suspended organic matter: 186.2 L/kg

Arithmetic mean K_om for sediment: 186.2 L/kg

Arithmetic mean 1/n: 0.903

Saturated vapour pressure: 3.03 x 10^-7 Pa (20 ºC)

Solubility in water: 2.8 mg/L (20 ºC)

Molecular mass: 383.59 g/mol

Active substance propamocarb-HCl:

Geometric mean DT₅₀ for degradation in water at 20°C: geomean of mean values from each notifier (15.7 and 18.5) = 17.0 days

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

Arithmetic mean K_om for suspended organic matter: 310.7 L/kg

Arithmetic mean K_om for sediment: 310.7 L/kg

Arithmetic mean 1/n: 0.867

Saturated vapour pressure: 8 x 10^-5 Pa (25ºC)

Solubility in water: 935 g/L (20°C, pH 7)

Molecular mass: 224.7 g/mol (propamocarb-HCl); 188.3 g/mol (propamocarb)

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.

In Table M.7a, the drift percentages and calculated surface water concentrations for the active substances fluopicolide and propamocarb-HCl for each intended use are presented.

Table M7a Overview of surface water concentrations for active substance fluopicolide and propamocarb-HCl in the edge-of-field ditch following spring application

Use

Substance

Rate a.s.

[kg/ha]

Freq.

Interval

Drift

[%]

PIEC

[mg/L]^*

PEC21

[mg/L]^*

PEC28

[mg/L]^*

Spring

spring

potatoes

Fluopicolide

Propamocarb-HCl

0.095

0.945

0.5

0.814

6.765

0.679

5.273

0.630

4.818

^*calculated according to TOXSWA

PECsediment

To address the risk to sediment organisms, a PEC sediment value is needed for fluopicolide.

The PECsediment values calculated with TOXSWA are expressed ing a.s./m³ sediment. This PECsed has to be converted to mg a.s./kg sed dw by dividing it by the dry weight (DW) bulk density.

It is assumed that the substance will be present mainly in the top 1 cm layer. This layer has a dry weight bulk density of 80 kg/m³. The maximum PEC value in sediment in the top 1 cm of sediment is reached at day 28 after application. See Table M.3b for calculation of PECsediment.

Table M.7b Maximum sediment concentration for active substance fluopicolide in the edge-of-field ditch following spring application

Use

Substance

Rate a.s.

[kg/ha]

drift

[%]

PECsediment

[g a.s./m³ sediment]^*

PECsediment

[mg a.s./kg sediment DW]^**

spring

potatoes

fluopicolide

0.095

0.5

0.246 x 10^-2

0.0308

* TOXSWA output

** calculated as (PECsed in g/m³ / 80 kg/m³)*1000 (conversion of g/kg to mg/kg)

The exposure concentrations in surface water and sediment 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.

fluopicolide

There are no data available in the Pesticide Atlas regarding the presence of the substance fluopicolide in surface water.

Propamocarb HCl

The active substance propamocarb HCl was observed in the surface water (most recent data from 2007). In Table M.8 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 630 µg/L (C-207.3.2/12, 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*NOECfish]) and to the indicative Maximum Permissible Concentration (MPC) of 190 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 application(s).

Table M.8 Monitoring data in Dutch surface water (from www.pesticidesatlas.nl, version 2.0)

Total no of locations

(2008)

n > authorisation threshold

n > indicative/ad hoc MPC threshold

n > MPC-INS threshold *

14**

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 ad hoc MPC value

** the number of observations at each location varies between 4 and 10, total number of measurements is 102 in 2008.

As there are no exceedings of thresholds, the monitoring data have no consequences for the proposed use of the product.

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.

Fluopicolide has been on the Dutch market for > 3 years (authorised since 01-06-2007). 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.

Propamocarb HCl has been on the Dutch market for > 3 years (authorised since 1990). 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

Fluopicolide

The vapour pressure is 3.03 x 10^-7 Pa at 20°C. The Henry constant is 4.15 x 10^-5 Pa m³ mol^-1 at 20°C. The half-life in air is 3.73 days assuming a 24 hour day.

Propamocarb-HCl

The vapour pressure is 8.1 x 10^-5 Pa and 1.66 x 10^-3 Pa at 25 ºC (two notifiers). The Henry constant is 8.5 x 10^-9 Pa.m³.mol^-1 at 20°C. The half-life in air is 4.03 and 13.4 hours (two notifiers).

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 end-points relating to the product and approved uses

See List of Endpoints.

6.5 Data requirements

None.

The following restriction sentences were proposed by the applicant:

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

None.

6.6 Overall conclusions fate and behaviour

It can be concluded that:

the active substances fluopicolide and propamocarb-HCl meet the standards for persistence in soil as laid down in the RGB.
metabolite M01 (BAM), of fluopicolide meets the standards for persistence in soil as laid down in the RGB.
all proposed applications of the active substances fluopicolide and propamocarb-HCl meet the standards for leaching to the shallow groundwater as laid down in the RGB.
all proposed applications of metabolites M01 (BAM), M02 and M03 of fluopicolide are declared non relevant and do not need to the standards for leaching to shallow groundwater as laid down in the RGB.
all proposed applications of the active substances fluopicolide and propamocarb-HCl meet the standards for surface water destined for the production of drinking water as laid down in the RGB.

7. Ecotoxicology

For the current application of Infinito, risk assessment is done in accordance with Chapter 2 of the RGB.

List of Endpoints Ecotoxicology

Fluopicolide

Fluopicolide is a new substance, included on Annex I. For the risk assessment the final LoEP of 06/2009 is used.

Formulation EXP 11120A contains 64.7 g fluopicoline/L and 634 g propamocarb-HCl/L. This formulation is used for the risk assessment of Infinito, containing 62.5 g fluopicoline/L and 625 g propamocarb-HCl/ha. This is acceptable, since formulation EXP 11120A is a comparable type of formulation and contains a higher concentration of a.s. and the ratio of the actives is about the same.

Effects on terrestrial vertebrates (Annex IIA, point 8.1, Annex IIIA, points 10.1 and 10.3)

Species	Test substance	Time scale	End point (mg/kg bw/day)	End point (mg/kg feed)
Birds ‡
C. virginianus	fluopicolide	Acute	>2250	-
C. virginianus	fluopicolide	Short-term	>1744	>5620
C. virginianus	Metabolite M01	Short-term	1171	3897
C. virginianus	fluopicolide	Long-term	88.9	1000
Mammals ‡
Rat	fluopicolide	Acute	>5000	-
Rat	EXP 11074B	Acute	>2000(product)	-
Rat	EXP 11120A	Acute	>2000(product)	-
Rat	Metabolite M01	Acute	M2000/F500	-
Rat	Metabolite M02	Acute	>5000	-
Rat	Metabolite M05	Acute	>5000	-
Rat	Metabolite M10	Acute	>5000	-
Rabbit	fluopicolide	Long-term	20.0
Additional higher tier studies ‡ - none

Toxicity data for aquatic species (most sensitive species of each group) (Annex IIA, point 8.2, Annex IIIA, point 10.2)

Group	Test substance	Time-scale (Test type)	End point	Toxicity¹ mg/L
Laboratory tests ‡
Fish
O. mykiss	fluopicolide	96h(static)	Mortality, LC₅₀	0.36^mm
P. pimales	fluopicolide	33d(flo thru)	Growth NOEC	0.155^mm
O. mykiss	EXP 11074B	96h(static)	Mortality, LC₅₀	0.39(8.54¹)^nom
O. mykiss	EXP 11120A	96h (static)	Mortality, LC₅₀	0.38(6.57¹)^nom
O. mykiss	Metabolite M01	96h (static)	Mortality, LC₅₀	240^nom
O. mykiss	Metabolite M02	96h (static)	Mortality, LC₅₀	>100^nom
O. mykiss	Metabolite M05	96h (static)	Mortality, LC₅₀	>100^nom
Aquatic invertebrate
D. magna	fluopicolide	48h (static)	Mortality, LC₅₀	>1.8^mm
D. magna	fluopicolide	21d (static ren)	Repro., NOEC	0.37^mm
D. magna	EXP 11074B	48h (static)	Mortality, LC₅₀	>1.13(>25¹)^nom
D. magna	EXP 11120A	48h (static)	Mortality, LC₅₀	>5.73(>100¹)^nom
D. magna	Metabolite M01	48h (static)	Mortality, LC₅₀	180^nom
Sediment dwelling organisms
C. riparius	fluopicolide	28d (static²)	Emergence,NOEC	49.0mg/kg^nom
Algae
Navicula pelliculosa	fluopicolide	72h (static)	Biomass: E_bC₅₀ Growth rate: E_rC₅₀	0.029^mm 0.069^mm
Navicula pelliculosa	EXP 11074B	72 h (static)	Biomass: E_bC₅₀ Growth rate: E_rC₅₀	0.026(0.58¹)^nom 0.041(0.91¹)^nom
Navicula pelliculosa	EXP 11120A	72 h (static)	Biomass: E_bC₅₀ Growth rate: E_rC₅₀	0.023(0.40¹)^nom 0.036(0.63¹)^nom
Navicula pelliculosa	Metabolite M01	72 h (static)	Biomass: E_bC₅₀ Growth rate: E_rC₅₀	>10.0^nom >10.0^nom
Navicula pelliculosa	Metabolite M05	72 h (static)	Biomass: E_bC₅₀ Growth rate: E_rC₅₀	>10.0^nom >10.0^nom
Higher plant
L. gibba G3	fluopicolide	7d (static)	Biomass: E_bC₅₀	>3.2^mm
L. gibba G3	Metabolite M01	7d (static)	Biomass: E_bC₅₀	>80.0^mm
Microcosm or mesocosm tests - not required

mm = mean measured; nom = nominal

¹ product; ² spiked sediment

Fish bioconcentration

Bioconcentration
	Fluopicolide
logP_O/W	2.9
Bioconcentration factor (BCF) ‡	121
Annex VI Trigger for the bioconcentration factor	100¹
Clearance time (days) (CT₅₀)	0.51
(CT₉₀)	1.7
Level and nature of residues (%) in organisms after the 14d depuration phase	5%

_{1 fish (ELS study) TERlt>10}

Effects on honeybees (Annex IIA, point 8.3.1, Annex IIIA, point 10.4)

Test substance	Acute oral toxicity LD₅₀ µg/bee	Acute contact toxicity LD₅₀ µg/bee
Fluopicolide ‡	>241	>100
EXP 11074B	>8.0¹ (>169²)	>3.3¹ (>70²)
EXP 11120A	>11.7¹ (>204²)	>8.2¹ (>143²)
Field or semi-field tests - not required

¹fluopicolide; ²preparation

Effects on other arthropod species (Annex IIA, point 8.3.2, Annex IIIA, point 10.5)

Laboratory tests with standard sensitive species

Species	Test Substance	End point	LR50 preparation
Typhlodromus pyri ‡	EXP 11074B	Mortality	7.13 kg/ha
Aphidius rhopalosiphi ‡	EXP 11074B	Mortality	8.23 kg/ha
Typhlodromus pyri ‡	EXP 11120A	Mortality	>8.0 L/ha
Aphidius rhopalosiphi ‡	EXP 11120A	Mortality	2.48 L/ha

Further laboratory and extended laboratory studies ‡

Species	Life stage	Test substance, substrate and duration	Dose (L/ha)¹	End point	(L/ha) % repro effect vs control¹	Trigger value
Aphidius rhopalosiphi	Adult	EXP 11120A Residues on leaves	1.0 2.0 4.0 8.0	Mortality LR50 Mean no. mummies/female	(>8.0) -7.6 -20.3 -50.0 -98.7	50 %
Typhlodromus pyri	Proto nymph	EXP 11120A Residues on leaves	0.4 0.72 1.29 2.32 4.17	Mortality LR50 Mean no. eggs & larvae /female	(>4.17) -12.9 -17.9 -27.6 -29.8 -34.3	50 %
Chrysoperla carnea	Larvae	EXP 11120A Glass plate test	6.4	Mortality LR50 Mean no. eggs/ female/d	(>6.4) -2.7	50 %
Field or semi-field tests - not required

¹ 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).

n.d. not determined, n.p. no assessment performed

Effects on earthworms, other soil macro-organisms and soil micro-organisms (Annex IIA points 8.4, 8.5 and 8.7, Annex IIIA, points, 10.6 and 10.7)

Soil macroorganisms

Test organism	Test substance	Test	End point (mg/kg soil)
Earthworms
	Fluopicolide ‡	Acute 14d LC50	>500¹
	Fluopicolide ‡	Chronic 56d NOEC	62.5¹ (28d growth)
	EXP 11074B	Acute 14d LC50	>21.75^2,4
	EXP 11074B	Chronic	2.435^2,4
	EXP 11120A	Acute 14d LC50	>28.65^2,4 Nl: note 1 is relevant, not note 2
	EXP 11120A	Chronic	2.587^2,4
	Metabolite M01	Acute 14d LC50	750³
	Metabolite M01	Chronic 56d NOEC	250³ (56d reproduction)
	Metabolite M02	Acute 14d LC50	>1000³
	Metabolite M03	Acute 14d LC50	>500¹
Other soil macro-organisms
Collembola
	Fluopicolide	28d NOEC	31.25¹
	Metabolite M01	28d NOEC	25.0³

¹ corrected endpoint (Log Pow>2; 10% w/w soil OM)

² correction not required (5% w/w/ soil OM)

³ correction not required (Log Pow <2)

Soil organisms – field studies

Field studies - Litter bag studies (soil organic matter degradation)
Test substance	Total soil conc.² mg/ kg d.wt. soil	max PECsoil mg/kg d.wt. soil (% soil conc/PEC)		% straw deg. vs. control [DAT]	EPFES 2002 trigger
		Potato	Vine
Fluopicolide¹	0.186	0.202³/0.112⁴ (92) / (166)	0.268³/0.134⁴ (69) / (139)	[29] +0.7 [92] -5.5 [184] -1.1	10%
M01	0.010	0.009³/0.017⁴ (90) / (59)	0.035³/0.017⁴ (29) / (59)	[29] +1.2 [92] -5.0 [184] -0.2	10%

¹ applied as SC480 formulation

² mean measured (10cm depth)

³ 5cm depth (worse case –no soil tillage); ⁴ 10cm depth

Soil microorganisms

Soil microbial test	Soil treatment	Test duration	Test rate (mg a.s./kg d.wt.soil)	Max. accum. PECsoil (mg a.s./kg d.wt.soil)³	% 28d deviation vs control (max % deviation)	Annex VI (%)
N-metabolism
	Fluopicolide ‡	28d	0.18¹/1.84²	0.268	+5(±5)/+7(-9)	25
	EXP 11074B	28d	0.178¹/1.775²	0.268	0(+4)/+11(-12)	25
	EXP 11120A	28d	0.18¹/1.80²	0.202	+7(+9)/+11(-16)	25
	Metabolite M01	14d	0.19/3.80	0.035	(-6)/(+11)	25
	Metabolite M01	28d	0.09/0.92	0.035	-2(-9)/-4(-13)	25
C-metabolism
	Fluopicolide ‡	28d	0.18¹/1.84²	0.268	-8(-8)/-6(-6)	25
	EXP 11074B	28d	0.178¹/1.775²	0.268	-7(-11)/-11(-15)	25
	EXP 11120A	28d	0.18¹/1.80²	0.202	-11(-14)/0(-10)	25
	Metabolite M01	14d	0.19/3.80	0.035	(±3)/(+2)	25
	Metabolite M01	28d	0.09/0.92	0.035	-8(-10)/-7(-10)	25

equivalent to ¹1x and ²10x fluopicolide field application rate

³ 5cm soil depth

Effects on non target plants (Annex IIA, point 8.6, Annex IIIA, point 10.8)

Preliminary screening data

Fluopicolide (20% w/w WP) - herbicidal screen - 27 crop/weed spp.

Post em - max. conc 1.28 kg/ha - no herbicidal effect - ER50>1.28kg/ha

Pre em - max. 1.28 mg kg soil - no herbicidal effect - ER50>1.707 mg/kg soil

EXP 11120A (taken from DAR): ER50 > 2.13 L/ha

Effects on biological methods for sewage treatment (Annex IIA 8.7)

Test type/organism	end point
Activated sludge (microbial respiration)	EC50 >25.4 mg fluopicolide/L

Ecotoxicologically relevant compounds (consider parent and all relevant metabolites requiring further assessment from the fate section)

Env Compartment	Compound
soil	fluopicolide
surface water	fluopicolide
sediment	fluopicolide
groundwater	fluopicolide

Classification and proposed labelling with regard to ecotoxicological data (Annex IIA, point 10 and Annex IIIA, point 12.3)

	RMS/peer review proposal
Active substance	N, R50, R53, S60, S61

	RMS/peer review proposal
EXP 11074B	N, R50, R53, S35, S57
EXP 11120A	N, R50, R53, S35, S57

Propamocarb-HCl

Propamocarb-HCl is placed on annex I (01-10-2007). For the risk assessment the final List of Endpoints from the EFSA scientific report (12/05/2006) is used.

It should be noted that all the values given in this section belong to propamocarb hydrochloride, a variant of propamocarb.

Effects on terrestrial vertebrates (Annex IIA, point 8.1, Annex IIIA, points 10.1 and 10.3)

Acute toxicity to mammals ‡	>1330 mg a.s./kg b.w./day
Long-term toxicity to mammals	104 mg a.s./kg b.w./day
Acute toxicity to birds ‡	>1842 mg a.s./kg b.w./day
Dietary toxicity to birds ‡	>962 mg a.s./kg b.w./day
Reproductive toxicity to birds ‡	105 mg a.s./kg b.w./day

Toxicity data for aquatic species (most sensitive species of each group) (Annex IIA, point 8.2, Annex IIIA, point 10.2)

Group	Test substance	Time-scale	Endpoint	Toxicity (mg/L)
Acute
Rainbow trout (Onchoryhynchus mykiss)	Propamocarb-HCl	96 hours	Mortality, LC50	>99
Bluegill Sunfish (Lepomis macrochirus)	Propamocarb-HCl	96 hours	Mortality, LC50	>92
Daphnia magna	Propamocarb-HCl	48 hours	Mortalities, EC50	>100
Pseudokirchneriella subcapitata	Propamocarb-HCl	72 hours	Growth Rate, EC50	>85
Lemna gibba	Propamocarb-HCl	14 days	Frond No., EC50	>18
Chronic
Bluegill sunfish (Lepomis macrochirus)	Propamocarb-HCl	32 days	NOEC	>6.3
Daphnia magna	Propamocarb-HCl	21 days	NOEC	12.3

Microcosm or mesocosm tests

Not required

Bioconcentration
Bioconcentration factor (BCF) ‡	Not required as Log P_ow<3
Annex VI Trigger: for the bioconcentration factor	>3
Clearance time (CT₅₀) (CT₉₀)	Not relevant
Level of residues (%) in organisms after the 14 day depuration phase	Not relevant

Effects on honeybees (Annex IIA, point 8.3.1, Annex IIIA, point 10.4)

Acute oral toxicity ‡	LD₅₀ >84 µg a.s./bee
Acute contact toxicity ‡	LD₅₀>100 µg a.s./bee

Effects on other arthropod species (Annex IIA, point 8.3.2, Annex IIIA, point 10.5)

Previcur N¹

Species	Stage	Study type	Toxicity Endpoints (g a.s./ha)
Species	Stage	Study type	LD/EC₅₀	LOEL	NOEL
Aphidius rhopalosiphi	Adults	Lab (glass)	500	500	170
Aphidius rhopalosiphi	Adults	Ext. Lab (barley)	>4315 CTB : >6500 *	>4315	4315
Diaeretiella rapae	Adults	Lab (glass)	>2190	>2190	<2190
Trichogramma caoeciae	Adults	Lab (glass)	790	790	-
Typhlodromus pyri	Adults	Lab (glass)	>360	>360	360
Typhlodromus pyri	Protonymphs/ Adults	Ext. Lab (lettuce)	>3 x 1450	>3 x 1450	3 x 1450
Aleochara bilineata	Adults	Lab (sand)	>9690	>9690	9690
Poecilus cupreus	Adults	Lab (sand)	>9690	>9690	9690
Chrysoperla carnea	2-3 day old larvae 2-3 day old larvae	Lab (glass)	>1080	>1080	<1080
Chrysoperla carnea	2-3 day old larvae	Ext. Lab (lettuce)	>3 x 1453	>3 x 1453	3 x 1453
Coccinella septempunctata	2-3 day old larvae	Lab (glass)	>1920	>1920	1920

* a mistake seems to have been made in the DAR: endpoint is > 9 L/ha, corresponding to >6500 kg a.s./ha

¹Previcur N = 720 g/L propamocarb-HCL

Field or semi-field tests

Not required

Proplant¹

Species	Stage	Test Substance	Dose (kg as/ha)	Endpoint	Adverse Effect²
Aphidius rhopalosiphi	Adults	Proplant	1.083*	Mortality / Fertility	32.6% +72.4%
Aphidius rhopalosiphi^#	Adults		3.450	Mortality / Fertility	9.1% +23.9%
Typhlodromus pyri	Protonymph/ Adult		1.083	Mortality / Fertility	-1.1% 21.1%
Coccinella septempunctata	Larvae		1.083	Mortality / Fertility	-3.5% 19.0%
Chrysoperla carnea	Larvae		1.083	Mortality / Fertility	-7.2% 10.04%
Poecilus cupreus	Adults		108.3	Mortality / Food consumption	3.6% +4.4%
Pardosa sp.^#	Adults		108.3	Mortality / Food consumption	0.0% +7.5%

¹ Test substance Proplant = 722 g propamocarb-HCl/L

² Adverse effect means:

x % effect on mortality = x % increase of mortality compared to control

y % effect on a sublethal parameter = y % decrease of sublethal parameter 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 effectpercentages (i.e. increase compared to control) and a – sign for mortality effectspercentages (i.e. decrease compared to control).

^#: extended lab (A. rhopalosiphi on barley seedlings, Pardosa sp. on soil), all others glass plate tests

Field or semi-field tests

Not required

Effects on earthworms (Annex IIA, point 8.4, Annex IIIA, point 10.6)

Acute toxicity ‡	LC₅₀ > 660 mg a.s./kg dry soil
Reproductive toxicity ‡	NOEC 362 mg a.s./kg dry soil

Effects on soil micro-organisms (Annex IIA, point 8.5, Annex IIIA, point 10.7)

Nitrogen mineralization ‡	No adverse effects up to 28.9 kg a.s./ha
Carbon mineralization ‡	No adverse effects up to 28.9 kg a.s./ha

Effects on non target plants (Annex IIA, point 8.6, Annex IIIA, point 10.8)

Preliminary screening data (Tier 1):

Previcur N had no phytotoxic effect on seed germination or vegetative vigour over a range of monocotyledons and dicotyledons that were exposed to a concentration of 9.18 kg Propamocarb HCl/ha.

Emergence of cucumber and wheat was adversely effected in a Tier I study at an exposure rate of 9.18 kg Propamocarb HCl/ha.

Dose Response Studies (Tier II):

Seedling emergence: Cucumber seedling emergence was significantly lower than the control at 27.54 and 82.62 kg a.s./ha (% effect ranged from –16% to +2%). There was no effect on this parameter in wheat.

Mean Length: In cucumber, mean length was significantly different in the highest treatment group. No effects were observed in wheat.

Dry weight: There was no significant different in the dry weight of either cucumber or wheat exposed to up to 82.62 kg a.s./ha.

Effects on biological methods for sewage treatment (Annex IIA 8.7)

Test type	Endpoint
Activated sludge	EC₅₀ (3h) >100 mg propamocarb HCl/L

Classification and proposed labelling (Annex IIA, point 10)

with regard to ecotoxicological data

R52 Harmful to aquatic organisms

S61 Avoid release to the environment. Refer to special instructions/Safety data sheets.

Combination toxicology

Combination toxicology is assessed for formulations containing more than one active substance, and for combinations of products, which are made according to the Instructions for Use as a tank mixture. Based on the precautionary principle, concentration-addition is assumed.

For pesticides the TER (Toxicity-Exposure Ratio) is used as a standard in the risk assessment (except for bees and other non-target arthropods, where HQ-values are calculated). The TER must be higher than a trigger value to comply with the standards.

For the combination risk assessment of formulations containing more than one active substance and for tank mixtures the following formula is used:

trigger_{substance 1} /TER_substance
1 + trigger_{substance 2}/TER_{substance 2}+ trigger_substance
i/TER_{substance i} .

When for each substance the trigger values are equal, the combined TER value can be calculated according to:

TER_combi= trigger/((trigger/TER_{substance 1})+(trigger/TER_{substance
2})+( trigger/TER_{substance 3}))

An acceptable risk is expected when TER_combi > trigger.

In case of unequal triggers, the combined TER value can be calculated using the following formula:

Trigger_combi = trigger_{substance 1}/trigger_{substance 2}/trigger_{substance
i}

TER_combi= trigger_combi/((trigger_{substance 1} /TER_{substance
1})+(trigger_{substance 2} /TER_{substance 2})+( trigger_{substance i} /TER_{substance i}))

An acceptable risk is expected when TER_combi > trigger_combi.

In this formula, ‘triggers’ are the trigger values as mentioned in the corresponding chapter of the HTB (v1.0).

In case toxicity of the formulation has been measured, the TER-value of the formulation is calculated with the PEC of the formulation and the toxicity value of the formulation. The PEC of the formulation is the sum of the PECs of the individual active substances. The toxicity value of the formulation is expressed in total amount active substance. Trigger/TER must be smaller than 1.

In the risk assessment, the risk of combination toxicology is assessed using the highest trigger/TER-value from the one based on the sum of the individual substances and the one based on formulation studies. When the standard of 1 is breached, the product is not permissable, unless an adequate risk assessment shows that there are no unacceptable effects under field conditions after application of the product according to the proposed GAP.

7.1 Effects on birds

Birds can be exposed to the active substances fluopicolide and propamocarb-HCl via natural food (sprayed insects, seeds, leafs), drinking water and as a result of secondary poisoning.

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

	Endpoint	Value
Fluopicolide
Acute toxicity to birds:	LD₅₀	>2250 mg a.s./kg bw
Dietary toxicity to birds:	LC₅₀	>1744 mg a.s./kg bw/d
Reproductive toxicity to birds:	NOEL	88.9 mg a.s./kg bw/d
Metabolite M01
Dietary toxicity to birds:	LC₅₀	1171 mg a.s./kg bw/d
Propamocarb-HCl
Acute toxicity to birds:	LD₅₀	>1842 mg a.s./kg bw
Dietary toxicity to birds:	LC₅₀	>962 mg a.s./kg bw/d
Reproductive toxicity to birds:	NOEL	105 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
potatoes	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) of both active substances 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
Fluopicolide		0.76	87	0.095	1.8	11.30	>2250	>199
Propamocarb-HCl		0.76	87	0.95	1.8	113	>1842	>16.3
combination								>15.0
	insectivorous bird
	Fluopicolide	1.04	52	0.095	-	5.14	>2250	>438
	Propamocarb-HCl	1.04	52	0.95	-	51.4	>1842	>35.8
	combination							>33.1

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
Fluopicolide		0.76	40	0.095	2.2	6.35	>1744	>274
Propamocarb-HCl		0.76	40	0.95	2.2	63.5	>962	>15.1
combination								>14.3
	insectivorous bird
	Fluopicolide	1.04	29	0.095	-	2.87	>1744	>609
	Propamocarb-HCl	1.04	29	0.95	-	28.7	>962	>33.6
	combination							>31.8

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
Fluopicolide		0.76	40	0.095	2.2	0.53	3.37	88.9	26.4
Propamocarb-HCl		0.76	40	0.95	2.2	0.53	33.7	105	3.12
combination									2.79
	insectivorous bird
	Fluopicolide	1.04	29	0.095	-	-	2.87	88.9	30.9
	Propamocarb-HCl	1.04	29	0.95	-	-	28.7	105	3.66
	combination								3.27

Taking the results in Table E.3 into account, it appears that based on the standard risk assessment, a long-term risk cannot be excluded. A further refinement is required.

Refined risk assessment

The first tier assessment is based on standard assumptions, in which whole fields are sprayed. However proposed application is non-professional use, which means a small scale application. It is therefore unlikely that birds will forage on such a very small scale for a long period.

Usually for non-professional uses the application rate is set on 1/10^th of the normal application rate (meaning that only 1/10^th of a hectare is sprayed). Therefore a correction factor of 0.1 is proposed for non-professional uses.

Additionally, potatoes are not a very attractive food source for herbivorous birds, although it cannot be excluded that weeds are available between the plants. Based on these arguments, it can be safely assumed that the long-term ETE for herbivorous birds will be about a factor of 10 lower that calculated above. This means that the TER values for herbivorous birds will be > 5.

Revised arthropod residue data became available when the Guidance Document for Birds and Mammals (Sanco 4145/2000) was revised. This document still has a draft status in the Netherlands, but a PPR-opinion of this GD by EFSA’s PPR-panel was published in June 2008 (Question No EFSA-Q-2006-064. The EFSA Journal (2008) 734:1-181). Based on the state of the art the Ctgb agrees to use the revised arthropod residue data as evaluated in the new GD as a higher tier in national risk assessment now that this EFSA opinion has become available. (NB: Other aspects of the new GD will not be used until official approval of the GD on national level.) The revised RUD values for arthropods are given in Table E.4 below (data taken from Appendix 14 to the EFSA opinion). Furthermore, it was determined that a generic DT₅₀ of 10 days can be used for arthropods. Based on this value, an ftwa of 0.53 can be used.

Table E.4 Revised RUD values for arthropods

Crop/category of insects	Crop stage	mean	90^th percentile
Ground dwelling invertebrates without interception¹	ground directed applications	7.5	13.8
Ground dwelling invertebrates with interception²	applications directed to crop canopies	3.5	9.7
Insects (foliar dwelling invertebrates³)	whole season	21.0	54.1

¹applications on bare soil, or ground directed applications up to principle growth stage 3, ground directed applications in orchards/vines (e.g. herbicides)

²applications directed to crop canopies (orchards/vines), ground directed applications on top of crops with principle growth stage of 4 or greater

³no data are available for canopy dwelling invertebrates in winter or before the leaves appear (interception would be less)

Table E.5 Refined long-term risk for birds

Substance		FIR / bw	RUD	Applica-tion rate (kg a.s./ha)	MAF	ftwa	Correction factor for non-professional use	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
Fluopicolide		0.76	40	0.095	2.2	0.53	0.1	3.37	88.9	264
Propamocarb-HCl		0.76	40	0.95	2.2	0.53	0.1	33.7	105	31.2
combination										27.9
	insectivorous bird
	Fluopicolide	1.04	21	0.095	-	0.53		0.11	88.9	80.8
	Propamocarb-HCl	1.04	21	0.95	-	0.53		1.10	105	9.6
	combination									8.5

Based on the calculations presented above, an acceptable risk is expected for birds.

No relevant plant metabolites were found for both active substances

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.

Fluopicolide

The highest PIEC_wateris 0.814 mg/L. It follows that the risk of drinking water is (LD50 * bw) / (PIEC*DWI) = (>2250 * 0.010) / (0.000814 * 0.0027) = >100000.

Since TER > 10, the risk is acceptable.

Propamocarb-HCl

The highest PIEC_wateris 6.77 mg/L. It follows that the risk of drinking water is (LD50 * bw) / (PIEC*DWI) = (>1842 * 0.010) / (0.00677 * 0.0027) = >100000.

Since TER > 10, the risk is acceptable.

Considering the high TER values, the combined risk is considered to be 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 fluopicolide and propamocarb-HCl < 3 (2.9 and -2.9 to 0.67 for pH range 2 to 9), the potential for bioaccumulation is considered low and no further assessment is deemed necessary. The metabolites of fluopicolide have Log Kow values lower than the parent. Therefore the risk to secondary poisoning is considered to be low.

Taking the results for secondary poisoning through fish and earthworms into account, the proposed use meet the standards for secondary poisoning as laid down in the RGB.

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.

Table E.6 Overview toxicity endpoints for aquatic organisms

Substance	Organism	Lowest		Toxicity value
		L(E)C₅₀ [mg a.s./L]	NOEC [mg/L]	[mg/L]
Fluopicolide	Acute
	Algae	0.029		29
	Daphnids	>1.8		>1800
	Fish	0.36		360
	Macrophytes	>3.2		>3200
	Chronic
	Daphnids		0.37	370
	Fish		0.155	155
M01	Acute
	Algae	>10		>10000
	Daphnids	-
	Fish	240		240000
	Macrophytes	>80		>80000
M02	Acute
	Fish	>100		>100000
M05	Acute
	Algae	>10		>10000
	Fish	>100		>100000
Propamocarb-HCl	Acute
	Algae	>85		>85000
	Daphnids	>100		>100000
	Fish	>92		>92000
	Macrophytes	>18		>18000
	Chronic
	Daphnids		12.3	12300
	Fish		6.3	6300
Formulation*	Acute
	Algae	0.279		279
	Daphnids	>69.87		>69870
	Fish	4.590		4590

*Expressed in total a.s.

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.7 TER values for aquatic organisms are shown.

Table E.7a TER values: 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
potatoes	Fluopicolide	0.814	35.6	>2211	442	>3931
	Propamocarb-HCl	6.77	>12555	>14771	>13589	>2659
	Combination		35.5	>1923	428	>1586
	Formulation	7.58	57.1	>9070	596

Table E. 7b TER values: chronic

Use	Substance	PECsw [mg a.s./L]	TER_lt (trigger 10)	TER_lt (trigger 10)
			Daphnid	Fish
potatoes	Fluopicolide	0.814	455	190
	Propamocarb-HCl	6.77	1817	931
	Combination		364	158

Taking the results in Table E.7a 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 substances fluopicolide and propamocarb-HCl the proposed uses meet the standards for aquatic organisms as laid down in the RGB.

Fluopicolide metabolites M01, M02 and M05 are less toxic than the parent by at least a factor 100. therefore the risk for the metabolites is also considered to be low.

7.2.2 Risk assessment for bioconcentration

Fluopicolide

For the active substance a BCF-value of 121 L/kg is available. This is just above the trigger of 100. The Log Pow is 2.9, which means that a BCF study is formally not required. The calculated value would be 58.2 L/kg, which is below the trigger of 100. Since fluopicolide also forms a low risk to birds, mammals and aquatic organisms (see sections 7.1.1, 7.2.1 and 7.3.1), the risk for bioconcentration is considered to be low.

Propamocarb-HCl

Since logKow of propamocarb-HCl is < 3 (for pH range 2 to 9: -2.9 to 0.67), experimental data are not required.

7.2.3 Risk assessment for sediment organisms

Fluopicolide

The NOEC value for Chironomus is 49.0 mg/kg. When this value is examined against the PIEC in sediment of 0.031 mg/kg, the TER value is 1581 mg/kg, which is above the trigger of 10. . Therefore, the active substance fluopicolide meets the standards for sediment organisms as laid down in the RGB.

Propamocarb-HCl

Propamocarb-HCl is relevant in sediment. However, since the NOEC for daphnids is > 0.1 mg a.s./L, the risk for sediment organisms is considered to be low.

Conclusions aquatic organisms

The proposed applications meet the standards for aquatic organisms.

7.3 Effects on terrestrial vertebrates other than birds

Mammals can be exposed to the active substances fluopicolide and propamocarb-HCl via natural food (sprayed insects, seeds, leafs), drinking water and as a result of secondary poisoning.

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.8 presents an overview of toxicity data.

Table E.8 Overview of toxicity data for mammals

	Endpoint	Value
Fluopicolide
Acute toxicity to mammals:	LD₅₀	>5000 mg a.s./kg bw
Reproductive toxicity to mammals:	NOEL	20 mg a.s./kg bw/d
Propamocarb-HCl
Acute toxicity to mammals:	LD₅₀	>1330 mg a.s./kg bw
Reproductive toxicity to mammals:	NOEL	104 mg a.s./kg bw/d
Formulation
Acute toxicity to mammals:	LD₅₀	>2000 mg form./kg bw

The formulation does not seem to pose a higher risk than the actives. No plant metabolites were considered relevant for risk assessment. Therefore the risk assessment will be performed for the active substances.

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.9 shows which indicator species are relevant for which uses.

Table E.9 Indicator species per use

Use	Crop	Indicator species
Potatoes	Leafy crops	Wood mouse*

* based on available field studies it was shown that the wood mouse is the most relevant species in potatoes (professional use). Thus, the use of a medium herbivorous mammal would underestimate the risk. Therefore first tier risk assessment will be performed with wood mouse. When assuming that the wood mouse only eats weeds, the FIR/bw is 1.68 (see Guidance document on birds and mammals, EFSA journal 2009, Appendix A). Although the proposed use is for non-professional use, the wood mouse can still be considered as worst-case species.

Table E.10a-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.10a 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)
Wood mouse
Fluopicolide	1.68	87	0.095	1.8	25.0	>5000	>200
Propamocarb-HCl	1.68	87	0.95	1.8	250	>1330	>5.32
combination							>5.18

Table E.10b 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)
Woodmouse
Fluopicolide	1.68	40	0.095	2.2	0.53	7.44	20	2.69
Propamocarb-HCl	1.68	40	0.95	2.2	0.53	74.4	104	1.40
combination								0.92

Taking the results in Table E.10 into account, it appears that a further refinement is required.

As for birds, a correction factor of 10 can be used, since only small areas are sprayed and since potato crops itself will not be eaten. With a correction factor of 10, the combined TER is 9.2, which is above the trigger of 5. Therefore the risk to mammals is acceptable.

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.

Fluopicolide

The highest PIEC_wateris 0.814 mg/L. It follows that the risk of drinking water is (LD50 * bw) / (PIEC*DWI) = (>5000 * 0.010) / (0.000814 * 0.00157) = >100000.

Since TER > 10, the risk is acceptable.

Propamocarb-HCl

The highest PIEC_wateris 6.77 mg/L. It follows that the risk of drinking water is (LD50 * bw) / (PIEC*DWI) = (>1330 * 0.010) / (0.00677 * 0.00157) = >100000.

Since TER > 10, the risk is acceptable.

Considering the high TER values for both actives, the combined risk is considered to be acceptable.

7.3.2 Secondary poisoning

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

Taking the results for secondary poisoning through fish and earthworms into account, the proposed use meet the standards for secondary poisoning as laid down in the RGB.

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 uses is given in Table E.13.

Table E.13 Risk for bees

Use	Substance	Application rate	LD₅₀	Rate/LD₅₀	Trigger value
		[g a.s./ha]	[µg a.s./bee]
potatoes	Fluopicolide	95	>100	<0.95	50
	Propamocarb-HCl	950	>84	<11.3	50
	Combination			<12.3
	Formulation	1045	>100	<1.05	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. The resulting Hazard Quotients are presented in Table E.14.

Table E.14 HQ-values for A. rhopalosiphi and T. pyri

	Application rate (L form/ha)	MAF¹	Drift factor/ Vegetation factor²	Safety factor²	LR₅₀ (L form/ha)	HQ
In-field
A. rhopalosiphi	1.5	2.7	-	-	2.48	1.63
T. pyri	1.5	2.7	-	-	>8.0	<0.51
Off-field
A. rhopalosiphi	1.5	2.7	0.0033	10	2.48	0.054
T. pyri	1.5	2.7	0.0033	10	>8.0	<0.017

¹: Multiple Application Factor

²: off-field: drift factor = 3.3% (default value non professional uses, hand-held spray application), vegetation distribution factor = 10, safety factor = 10 (default values)

As the above table shows, both in- and off-field HQ values are below the trigger value of 2.

The proposed application of the product therefore meets with the standards as laid down in the RGB.

Additionally a study with Chrysoperla carnea is available. No effects were found at a dose of 6.4 L/ha, which is higher than proposed use.

Hence, the standards for non-target arthropods as laid down in the RGB are met.

7.5.2 Earthworms

The acute risk for earthworms is calculated as TER-value(trigger value 10). Since the logPow of the active substance fluopicolide and metabolite M03 > 2, a correction to the reference soil containing 4.7 % organic matter is necessary. For Propamocarb-HCl and the metabolite M01 and no correction is required, since the Log Pow < 2. For the formulation no correction is required since the test was performed at 5% o.m. Exposure is expressed as the initial PEC soil. PEC soil is calculated in section 6.1.1. Table E.15 presents endpoints, PECsoil and TER values.

Table E.15 Overview of soil concentrations and acute TERs for earthworms

Use	Substance	LC50_corr [mg a.s./kg]	PIECsoil [mg/kg]	TER	Trigger value
potatoes	Fluopicolide M01 M03	>500 750 >500	0.243 0.063 0.01	>2058 11905 >50000	10
	Propamocarb-HCl	>660	2.39	>276	10
	Combination			243	10
	Formulation	>328*	2.63	>125	10

*total a.s.

In view of the results presented in Table E.16, 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.16.

Table E.16 Overview of soil concentrations and chronic TERs for earthworms

Use	Substance	NOEC [mg/kg]	PIECsoil [mg/kg]	TER	Trigger value
potatoes	Fluopicolide M01	62.5* 250	0.243 0.063	257 3968	5
	Propamocarb-HCl	362	2.39	151	5
	Combination			95.3	5
	Formulation	27.9**	2.63	10.6	5

*test with 5% o.m.

**total a.s.

The chronic threshold value for earthworms resulting from exposure to the active substances, metabolite M01 and the formulation is not exceeded. The proposed application of the product therefore meets the standards as laid down in the RGB.

7.5.3 Effects on soil micro-organisms

In the tested soils no effects are observed on nitrogen transformation and carbon respiration processes at relevant application rates with the active substance fluopicolide and propamocarb-HCl, metabolite M01 and formulation EXP 11120A. Since the reduction percentage is below 25% after 28 days, the standards from the RGB regarding soil micro-organisms are met.

7.5.4 Effects on activated sludge

An EC₅₀ value of >25.4 mg/L is available for fluopicolide and an EC50 of > 100 mg/L is available for Propamocarb-HCl.

However, for the proposed uses 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 3.3%. The exposure thus equals 0.033 * the application rate * MAF (in case of multiple application). MAF-values are taken from ESCORT 2.

In the DAR initial screening data are given. For formulation EXP 1120A (64.7 g/L fluopicolide and 634 g/L propamocarb-HCl) a maximum effect of 25% was found at the maximum dose of 2.13 L/ha. The EC50 is thus > 2.13 L/ha.

See table E.17 for TER calculation.

Table E.17 Overview of exposure concentrations and TERs for non target plants

Use

Substance

Dose

[L form. /ha]

MAF

Drift% (off-field exposure)

Exposure

(L form./ha)

EC₅₀

[L form./ha]

TER

Trigger value

Potatoes

Infinito

1.5

2.7

3.3

0.13

>2.13

>15.9

The ratio between EC₅₀ and the exposure concentration is > 5. Therefore, the risk for non-target plants is considered to be low.

The product complies with the RGB.

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 end-points relating to the product and approved uses

See List of Endpoints.

7.7 Data requirements

7.8 Classification and Labelling

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 characteristics of the co-formulants, the following labeling of the preparation is proposed:

Symbol:	N	Indication of danger:	Dangerous for the environment.
R phrases	50/53	Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment.

S phrases	29	Do not empty into drains.

Explanation:
Hazard symbol:	-
Risk phrases:	Based on the EbC50 of 0.40 mg product/L from the study with the formulated product and the algal species N. pelliculosa (see LoE fluopicolide), classification is R50/53.
Safety phrases:	S29 is prescribed for products for non-professional use.with R50/53.
Other:	-

The following restriction sentences were proposed by the applicant:

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

In the WG (legal instructions):

7.9 Overall conclusions regarding ecotoxicology

It can be concluded that:

the proposed application of the formulated product Infinito meets the standards for birds as laid down in the RGB.
the proposed application of the formulated product Infinito meets the standards for aquatic organisms as laid down in the RGB.
the active substance fluopicolide meets the standards for bioconcentration as laid down in the RGB.
the active substance propamocarb-HCl meets the standards for bioconcentration as laid down in the RGB.
the proposed application of the formulated product Infinito meets the standards for mammals as laid down in the RGB.
the proposed application of the formulated product Infinito meets the standards for bees as laid down in the RGB.
the proposed application of the formulated product Infinito meets the standards for non-target arthropods as laid down in the RGB.
the proposed application of the formulated product Infinito meets the standards for earthworms as laid down in the RGB.
the proposed application of the formulated product Infinito meets the standards for soil micro-organisms as laid down in the RGB.
the proposed application of the formulated product Infinito meets the standards for activated sludge as laid down in the RGB.
the proposed application of the formulated product Infinito meets the standards for non-target plants as laid down in the RGB

8. Efficacy

Infinito is already authorised in The Netherlands for professional use. Claimed is the extension to non-professional use. Dose rate and application is the same for both uses. As a consequence evaluation of efficacy is not necessary.

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:	N	Indication of danger:	Dangerous for the environment.
	Xi	Indication of danger:	Irritating
R phrases	R 43	May cause sensitisation by skin contact.
	R 50/53	Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment.
S phrases	S 2	Keep out of the reach of children.
	S 21	When using do not smoke.
	S 29	Do not empty into drains.

Special provisions: DPD-phrases³	-	-

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.

Veiligheidstermijn

De termijn tussen de laatste toepassing en de oogst mag niet korter zijn dan: 7 dagen.

[1] X This column is reserved for any other property that is considered to have a particular impact on the degradation rate.

[2] X This column is reserved for any other property that is considered to have a particular impact on the degradation rate.

[3] X This column is reserved for any other property that is considered to have a particular impact on the degradation rate.

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

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

[6] 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’.

werkzame stof:	gehalte:
fluopicolide	62,5 g/l
propamocarb	525,2 g/l

gevaarsymbool:	aanduiding:
Xi	Irriterend
N	Milieugevaarlijk

Algemeen

Toepassingen

Calculation of the ADI

Calculation of the ADI

Calculation of the ADI

Propamocarb-HCl

PECsediment

Chronic

Chronic

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*	Data protection	Study Used? Y/N
KIIIA 2.7.1/01	M Faers	2009	Infinito. Stability of Infinito in 100 ml HDPE bottles. Bayer CropScience BV M-352822-01-1 GLP: not applicable Unpublished ...also filed: KIIIA 2.7.2/01 ...also filed: KIIIA 2.7.3/01 ...also filed: KIIIA 2.7.4/01 ...also filed: KIIIA 2.7.5/01 ...also filed: KIIIA 2.7.6/01	Y	Bayer CropScience BV	12927 N	This submission	5 years after authorisation of this extension	Y
KIIIA 2.7.2/01	M Faers	2009	Infinito. Stability of Infinito in 100 ml HDPE bottles. Bayer CropScience BV M-352822-01-1 GLP: not applicable Unpublished ...also filed: KIIIA 2.7.1/01 ...also filed: KIIIA 2.7.3/01 ...also filed: KIIIA 2.7.4/01 ...also filed: KIIIA 2.7.5/01 ...also filed: KIIIA 2.7.6/01	Y	Bayer CropScience BV	12927 N	This submission	5 years after authorisation of this extension	Y
KIIIA 2.7.3/01	M Faers	2009	Infinito. Stability of Infinito in 100 ml HDPE bottles. Bayer CropScience BV M-352822-01-1 GLP: not applicable Unpublished ...also filed: KIIIA 2.7.1/01 ...also filed: KIIIA 2.7.2/01 ...also filed: KIIIA 2.7.4/01 ...also filed: KIIIA 2.7.5/01 ...also filed: KIIIA 2.7.6/01	Y	Bayer CropScience BV	12927 N	This submission	5 years after authorisation of this extension	Y
KIIIA 2.7.4/01	M Faers	2009	Infinito. Stability of Infinito in 100 ml HDPE bottles. Bayer CropScience BV M-352822-01-1 GLP: not applicable Unpublished ...also filed: KIIIA 2.7.1/01 ...also filed: KIIIA 2.7.2/01 ...also filed: KIIIA 2.7.3/01 ...also filed: KIIIA 2.7.5/01 ...also filed: KIIIA 2.7.6/01	Y	Bayer CropScience BV	12927 N	This submission	5 years after authorisation of this extension	Y
KIIIA 2.7.5/01	M Faers	2009	Infinito. Stability of Infinito in 100 ml HDPE bottles. Bayer CropScience BV M-352822-01-1 GLP: not applicable Unpublished ...also filed: KIIIA 2.7.1/01 ...also filed: KIIIA 2.7.2/01 ...also filed: KIIIA 2.7.3/01 ...also filed: KIIIA 2.7.4/01 ...also filed: KIIIA 2.7.6/01	Y	Bayer CropScience BV	12927 N	This submission	5 years after authorisation of this extension	Y
KIIIA 2.7.6/01	M Faers	2009	Infinito. Stability of Infinito in 100 ml HDPE bottles. Bayer CropScience BV M-352822-01-1 GLP: not applicable Unpublished ...also filed: KIIIA 2.7.1/01 ...also filed: KIIIA 2.7.2/01 ...also filed: KIIIA 2.7.3/01 ...also filed: KIIIA 2.7.4/01 ...also filed: KIIIA 2.7.5/01	Y	Bayer CropScience BV	12927 N	This submission	5 years after authorisation of this extension	Y